m6A Regulator Information

General Information of the m6A Regulator (ID: REG00005)

Regulator Name	RNA demethylase ALKBH5 (ALKBH5)
Synonyms	Alkylated DNA repair protein alkB homolog 5; Alpha-ketoglutarate-dependent dioxygenase alkB homolog 5; ABH5; OFOXD1 Click to Show/Hide
Gene Name	ALKBH5
Sequence	MAAASGYTDLREKLKSMTSRDNYKAGSREAAAAAAAAVAAAAAAAAAAEPYPVSGAKRKY QEDSDPERSDYEEQQLQKEEEARKVKSGIRQMRLFSQDECAKIEARIDEVVSRAEKGLYN EHTVDRAPLRNKYFFGEGYTYGAQLQKRGPGQERLYPPGDVDEIPEWVHQLVIQKLVEHR VIPEGFVNSAVINDYQPGGCIVSHVDPIHIFERPIVSVSFFSDSALCFGCKFQFKPIRVS EPVLSLPVRRGSVTVLSGYAADEITHCIRPQDIKERRAVIILRKTRLDAPRLETKSLSSS VLPPSYASDRLSGNNRDPALKPKRSHRKADPDAAHRPRILEMDKEENRRSVLLPTHRRRG SFSSENYWRKSYESSEDCSEAAGSPARKVKMRRH Click to Show/Hide
Family	alkB family
Function	Dioxygenase that demethylates RNA by oxidative demethylation: specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes. Can also demethylate N(6)-methyladenosine in single-stranded DNA (in vitro). Requires molecular oxygen, alpha-ketoglutarate and iron. Demethylation of m6A mRNA affects mRNA processing and export. Required for the late meiotic and haploid phases of spermatogenesis by mediating m6A demethylation in spermatocytes and round spermatids: m6A demethylation of target transcripts is required for correct splicing and the production of longer 3'-UTR mRNAs in male germ cells (By similarity). Click to Show/Hide
Gene ID	54890
Uniprot ID	ALKB5_HUMAN
Regulator Type	WRITER ERASER READER
Mechanism Diagram	Click to View the Original Diagram

Target Genes	Click to View Potential Target Genes of This Regulator

Full List of Target Gene(s) of This m6A Regulator and Corresponding Disease/Drug Response(s)

ALKBH5 can regulate the m6A methylation of following target genes, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulted from the regulation of certain target gene.

Browse Target Gene related Disease

Browse Target Gene related Drug

Alpha-enolase (ENO1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	human pluripotent stem cells	Homo sapiens
Treatment: hILO ALKBH5knockout cells Control: hILO wild type cells		GSE163945
Regulation		logFC: -9.52E-01 p-value: 3.98E-04
More Results	Click to View More RNA-seq Results

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[1]
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulation	Down regulation
Pathway Response	Carbon metabolism			hsa01200
Pathway Response	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glycolysis
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	NCI-H441	Lung papillary adenocarcinoma	Homo sapiens	CVCL_1561
	NCI-H292	Lung mucoepidermoid carcinoma	Homo sapiens	CVCL_0455
	NCI-H2030	Lung adenocarcinoma	Homo sapiens	CVCL_1517
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	3LL	Malignant tumors of the mouse pulmonary system	Mus musculus	CVCL_5653
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	Calu-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0608
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A-427	Lung adenocarcinoma	Homo sapiens	CVCL_1055
	16HBE14o-	Normal	Homo sapiens	CVCL_0112
In-vivo Model	KP and Mettl3^-/- mice were bred to generate KPM^-/- mice. Afterwards, the KP and KPM^-/- mice were intranasally infected under anesthesia with adeno-associated virus type 5 (AAV5) expressing Cre to initiate lung tumorigenesis along with ALKBH5-expressing AAV5 or Empty AAV5 to generate KPE, KPA, KPEM^-/- and KPAM^-/- spontaneous LUAD mouse models. For generation of LLC-based intra-pulmonary tumor mouse models, 1 × 10⁷ LLC cells were injected into C57BL/6 mice via the tail vein.For cell-derived xenograft (CDX) mouse models, 1.0 × 10⁷ H1299 or 1.5 × 10⁷ H1975 cells were subcutaneously injected into 4-6-week-old athymic nude mice. The tumors were monitored at indicated time points and isolated for further analysis after sacrifice.
Response Summary	Alpha-enolase (ENO1) positively correlated with METTL3 and global m6A levels, and negatively correlated with ALKBH5 in human Lung adenocarcinoma(LUAD). In addition, m6A-dependent elevation of ENO1 was associated with LUAD progression.

Apoptosis regulator Bcl-2 (BCL2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	CAG cell line	Homo sapiens
Treatment: shALKBH5 CAG cells Control: shNC CAG cells		GSE180214
Regulation		logFC: -7.25E-01 p-value: 1.10E-04
More Results	Click to View More RNA-seq Results

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[2]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
In-vitro Model	A2780	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	CoC1	Ovarian adenocarcinoma	Homo sapiens	CVCL_6891
	OVCAR-3	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0465
	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In-vivo Model	SKOV3 or A2780 cells were infected with the indicated lentiviral vectors and injected (5 × 10⁶ cells/mouse in 200 uL volume) subcutaneously into the left armpit of 6-week-old BALB/c nude mice. After 21 days, the animals were sacrificed to confirm the presence of tumors and weigh the established tumors
Response Summary	ALKBH5 is a tumor-promoting gene in epithelial ovarian cancer, which is involved in the mTOR pathway and Apoptosis regulator Bcl-2 (BCL2)-Beclin1 complex. ALKBH5 activated EGFR-PIK3CA-AKT-mTOR signaling pathway. ALKBH5 inhibited autophagy of epithelial ovarian cancer through miR-7 and BCL-2.

Aurora kinase B (AURKB)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	HaCAT cell line	Homo sapiens
Treatment: siALKBH5 HaCAT cells Control: siControl HaCAT cells		GSE211076
Regulation		logFC: 9.68E-01 p-value: 1.88E-24
More Results	Click to View More RNA-seq Results

Renal cell carcinoma [ICD-11: 2C90]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[3]
Responsed Disease	Renal cell carcinoma [ICD-11: 2C90]
Target Regulation	Up regulation
Pathway Response	HIF-1 signaling pathway			hsa04066
Cell Process	Cell proliferation
	Cell colony formation
	Cell migration
	Cell invasion
In-vitro Model	769-P	Renal cell carcinoma	Homo sapiens	CVCL_1050
	786-O	Renal cell carcinoma	Homo sapiens	CVCL_1051
	ACHN	Papillary renal cell carcinoma	Homo sapiens	CVCL_1067
	Caki-1	Clear cell renal cell carcinoma	Homo sapiens	CVCL_0234
	Caki-2	Papillary renal cell carcinoma	Homo sapiens	CVCL_0235
	HK2	Normal	Acipenser baerii	CVCL_YE28
In-vivo Model	The nude mice were randomly grouped into 2 groups, of 5 mice each; 786-0 cells (7×10⁶ in 100 L PBS) were stabilized with ALKBH5 knockdown lentiviral transfection vector (shALKBH5) or scramble vector (SCR) via subcutaneous injection into the left armpit of each mouse.
Response Summary	ALKBH5 plays a carcinogenic role in renal cell carcinoma by stabilizing Aurora kinase B (AURKB) mRNA in a m6A-dependent manner.

Beclin-1 (BECN1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: -1.52E+00 p-value: 9.98E-13
More Results	Click to View More RNA-seq Results

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[2]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
In-vitro Model	A2780	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	CoC1	Ovarian adenocarcinoma	Homo sapiens	CVCL_6891
	OVCAR-3	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0465
	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In-vivo Model	SKOV3 or A2780 cells were infected with the indicated lentiviral vectors and injected (5 × 10⁶ cells/mouse in 200 uL volume) subcutaneously into the left armpit of 6-week-old BALB/c nude mice. After 21 days, the animals were sacrificed to confirm the presence of tumors and weigh the established tumors
Response Summary	ALKBH5 is a tumor-promoting gene in epithelial ovarian cancer, which is involved in the mTOR pathway and BCL-2-Beclin-1 (BECN1) complex. ALKBH5 activated EGFR-PIK3CA-AKT-mTOR signaling pathway. ALKBH5 inhibited autophagy of epithelial ovarian cancer through miR-7 and BCL-2.

Bone morphogenetic protein 2 (BMP2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: 9.58E-01 p-value: 1.09E-02
More Results	Click to View More RNA-seq Results

Ossification of spinal ligaments [ICD-11: FA83]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[4]
Responsed Disease	Ossification of spinal ligaments [ICD-11: FA83]
Responsed Drug	MK22606	Investigative	Drug Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway		hsa04151
Cell Process	Ossification
In-vitro Model	Ligamentum flavum cells (Ligamentum flavum cells)
Response Summary	The overexpression of ALKBH5 led to the activation of p-AKT, and Bone morphogenetic protein 2 (BMP2) was regulated by ALKBH5 through the AKT signaling pathway. ALKBH5 promoted the osteogenesis of the ligamentum flavum cells through BMP2 demethylation and AKT activation. MK22606 is an AKT inhibitor. Moreover, when ALKBH5 was knocked down in the ligamentum flavum cells, p-AKT was inhibited when compared with that in the overexpressed ALKBH5 and control groups.

Breast cancer type 1 susceptibility protein (BRCA1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	HaCAT cell line	Homo sapiens
Treatment: siALKBH5 HaCAT cells Control: siControl HaCAT cells		GSE211076
Regulation		logFC: 7.57E-01 p-value: 2.32E-06
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[5]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	HCC1937	Breast ductal carcinoma	Homo sapiens	CVCL_0290
In-vivo Model	For the subcutaneously transplanted tumor model, wild-type, PRMT5-overexpressing or doxorubicin-resistant MDA-MB-231 cells (5 × 10⁶ per mouse, n = 5-7 for each group) were diluted in 100 uL of phosphate-buffered saline (PBS) plus 100 uL of Matrigel (BD Biosciences) and subcutaneously injected into female nude mice to investigate tumor growth. When all tumor volumes reached 100 mm³, the mice were randomly assigned and treated with the indicated drugs. In the experiment, doxorubicin was administered once a week via intravenous tail vein injection at 2 mg/kg body weight, and tadalafil was administered daily via oral gavage at 2 mg/kg body weight. Tumor volume was measured every 3 days using a digital caliper and calculated using the formula V = 1/2 × (diameter) × (smaller diameter)2. The mice were euthanized 27 days after injection.
Response Summary	ALKBH5 removed the m6A methylation of Breast cancer type 1 susceptibility protein (BRCA1) for mRNA stabilization and further enhanced DNA repair competency to decrease doxorubicin efficacy in breast cancer cells.

Catenin beta-1 (CTNNB1/Beta-catenin)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: -1.63E+00 p-value: 8.42E-15
More Results	Click to View More RNA-seq Results

Spina bifida [ICD-11: LA02]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[6]
Responsed Disease	Neural tube defect [ICD-11: LA02.Z]
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Cell apoptosis
In-vitro Model	HT22	Normal	Mus musculus	CVCL_0321
In-vivo Model	The mice were maintained on a 12-h light/dark cycle (lights on from 8:00 a.m. to 8:00 p.m.). On day 7.5 of pregnancy (E7.5), ethionine (Sigma-Aldrich, USA) was intraperitoneally injected only once at a dose of 500 mg/kg to establish the NTDs embryo model. And SAM (MedChemExpress, USA) was intraperitoneally injected only once at a dose of 30 mg/kg. The same dose was intraperitoneally injected to the pregnant mice for control group.
Response Summary	SAM not only played a compensatory role, but also led to m6A modification changes in neural tube development and regulation. Ethionine affected m6A modification by reducing SAM metabolism. METTL3 is enriched in HT-22 cells, and METTL3 knockdown reduces cell proliferation and increases apoptosis through suppressing Wnt/Catenin beta-1 (CTNNB1/Beta-catenin) signaling pathway. Overexpression of ALKBH5 can only inhibit cell proliferation, but cannot promote cell apoptosis.

CUB domain-containing protein 1 (CDCP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: 1.57E+00 p-value: 8.38E-14
More Results	Click to View More RNA-seq Results

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[7]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Down regulation
In-vitro Model	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	RWPE-1	Normal	Homo sapiens	CVCL_3791
	NSTC2 (Nickel-induced transformation of human cells)
	MC-SV-HUC T-2	Ureteral tumor cell	Homo sapiens	CVCL_6418
	16HBE14o-	Normal	Homo sapiens	CVCL_0112
In-vivo Model	To test for malignant transformation, 1×10⁷ cells were inoculated subcutaneously in the dorsal thoracic midline of ten NOD/SCID mice (Weitong Lihua Experimental Animal Technology Co. Ltd). Tumor formation and growth were assessed every 3 days.
Response Summary	m6A methyltransferase METTL3 and demethylases ALKBH5 mediate the m6A modification in 3'-UTR of CDCP1 mRNA. METTL3 and CUB domain-containing protein 1 (CDCP1) are upregulated in the bladder cancer patient samples and the expression of METTL3 and CDCP1 is correlated with the progression status of the bladder cancers.

Cyclin-dependent kinase inhibitor 1 (CDKN1A)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	CAG cell line	Homo sapiens
Treatment: shALKBH5 CAG cells Control: shNC CAG cells		GSE180214
Regulation		logFC: -1.90E+00 p-value: 1.35E-05
More Results	Click to View More RNA-seq Results

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Down regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Arrest cell cycle at G1 phase
In-vitro Model	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	NCI-H2087	Lung adenocarcinoma	Homo sapiens	CVCL_1524
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	ABC-1	Lung adenocarcinoma	Homo sapiens	CVCL_1066
	NCI-H358	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1559
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	HEK293	Normal	Homo sapiens	CVCL_0045
	PC-3 [Human lung carcinoma]	Lung adenocarcinoma	Homo sapiens	CVCL_S982
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	RERF-LC-MS	Lung adenocarcinoma	Homo sapiens	CVCL_1655
	HLC-1	Lung adenocarcinoma	Homo sapiens	CVCL_5529
	LC-2/ad	Lung adenocarcinoma	Homo sapiens	CVCL_1373
Response Summary	The expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A) or TIMP3 was increased by ALKBH5 knockdown. In conclusions, the ALKBH5-IGF2BPs axis promotes cell proliferation and tumorigenicity, which in turn causes the unfavorable prognosis of NSCLC.

Oral cavity/oesophagus/stomach in situ carcinoma [ICD-11: 2E60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[9]
Responsed Disease	Esophageal squamous cell carcinoma [ICD-11: 2B70.1]
Target Regulation	Down regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell cycle
Cell Process	Cell apoptosis
In-vitro Model	OE21	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_2661
	TE-1	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
	TE-5	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1764
	TE-9	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1767
In-vivo Model	The OE21 cells were stably transfected with sh-ALKBH5 (#1), sh-ALKBH5 (#2) or sh-scramble as negative control and injected (2 × 10⁶ cells/mouse in 100 uL volume) subcutaneously into the back of male athymic BALB/c nude mice (6 weeks old, Japan SLC).
Response Summary	Expression of CDKN1A (p21) was significantly up-regulated in ALKBH5-depleted cells, and m6 A modification and stability of Cyclin-dependent kinase inhibitor 1 (CDKN1A) mRNA were increased by ALKBH5 knockdown. Identify ALKBH5 as the first m6 A demethylase that accelerates cell cycle progression and promotes cell proliferation of ESCC cells, which is associated with poor prognosis of esophageal squamous cell carcinoma patients.

DNA (cytosine-5)-methyltransferase 3B (DNMT3B)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: 1.42E+00 p-value: 9.24E-11
More Results	Click to View More RNA-seq Results

Intervertebral disc degeneration [ICD-11: FA80]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[10]
Responsed Disease	Intervertebral disc degeneration [ICD-11: FA80]
Target Regulation	Down regulation
In-vitro Model	Nucleus pulposus cell (The NP tissues were cut into pieces after collection during surgery)
Response Summary	Theses findings reveal an epigenetic interplay mechanism in NPC senescence and IVD degeneration, presenting a critical pro-senescence role of ALKBH5 and m6A hypomethylation, highlighting the therapeutic potential of targeting the m6A/DNA (cytosine-5)-methyltransferase 3B (DNMT3B)/E4F1 axis for treating IVD degeneration.

E3 ubiquitin-protein ligase BRE1B (RNF40)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	NOMO-1 cell line	Homo sapiens
Treatment: shALKBH5 NOMO-1 cells Control: shNS NOMO-1 cells		GSE144968
Regulation		logFC: 6.81E-01 p-value: 5.37E-04
More Results	Click to View More RNA-seq Results

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[11]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Up regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Proteasome pathway degradation
In-vitro Model	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	OS-17	Osteosarcoma	Homo sapiens	CVCL_9992
	IMR-90	Normal	Homo sapiens	CVCL_0347
	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
	143B	Osteosarcoma	Homo sapiens	CVCL_2270
In-vivo Model	For tumor xenograft studies, 143B cells stably expressing scrambled shRNA or ALKBH5 shRNA (1 × 10⁶) were injected subcutaneously into the flanks of 4-week-old athymic nude mice.
Response Summary	In osteosarcoma, ALKBH5 mediates its protumorigenic function by regulating m6A levels of histone deubiquitinase USP22 and the ubiquitin ligase E3 ubiquitin-protein ligase BRE1B (RNF40).

eIF4E-binding protein 1 (4EBP1/EIF4EBP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	MOLM-13 cell line	Homo sapiens
Treatment: shALKBH5 MOLM-13 cells Control: shNS MOLM-13 cells		GSE144968
Regulation		logFC: -7.12E-01 p-value: 2.44E-03
More Results	Click to View More RNA-seq Results

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[12]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	HL-60	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	HL-60 cells (1 × 10⁷) suspended in 0.1 ml PBS containing 50% Matrigel were subcutaneously injected into the flanks of the mice. When tumor sizes reached 200 mm³, the mice were randomly distributed into four groups with the indicated dosages of saline, cytarabine and BP alone or in combination. For BP injections, the solution was delivered intraperitoneally at 106 ug/kg body weight for the first 8 consecutive days. For cytarabine injections, the solution was delivered intraperitoneally at 100 mg/kg body weight three times (once every three days). The combination group was administered intraperitoneally three times (once every three days) with the same dosages as described above. The control group was treated with an equivalent amount of saline.
Response Summary	Bioactive peptides can inhibit acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m6A demethylation of eIF4E-binding protein 1 (4EBP1/EIF4EBP1) and MLST8 mRNAs, which have potential to prevent and treat this disease.

Epidermal growth factor receptor (EGFR)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: 9.50E-01 p-value: 4.65E-04
More Results	Click to View More RNA-seq Results

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[2]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Pathway Response	mTOR signaling pathway			hsa04150
In-vitro Model	A2780	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	CoC1	Ovarian adenocarcinoma	Homo sapiens	CVCL_6891
	OVCAR-3	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0465
	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In-vivo Model	SKOV3 or A2780 cells were infected with the indicated lentiviral vectors and injected (5 × 10⁶ cells/mouse in 200 uL volume) subcutaneously into the left armpit of 6-week-old BALB/c nude mice. After 21 days, the animals were sacrificed to confirm the presence of tumors and weigh the established tumors
Response Summary	ALKBH5 is a tumor-promoting gene in epithelial ovarian cancer, which is involved in the mTOR pathway and BCL-2-Beclin1 complex. ALKBH5 activated Epidermal growth factor receptor (EGFR)-PIK3CA-AKT-mTOR signaling pathway. ALKBH5 inhibited autophagy of epithelial ovarian cancer through miR-7 and BCL-2.

F-box/LRR-repeat protein 5 (FBXL5)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	human pluripotent stem cells	Homo sapiens
Treatment: hILO ALKBH5knockout cells Control: hILO wild type cells		GSE163945
Regulation		logFC: -8.45E-01 p-value: 2.55E-03
More Results	Click to View More RNA-seq Results

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[13]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Target Regulation	Up regulation
Pathway Response	Adherens junction			hsa04520
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
Response Summary	ALKBH5 overexpression incurred a significant reduction in iron-regulatory protein IRP2 and the modulator of epithelial-mesenchymal transition (EMT) SNAI1. Owing to F-box/LRR-repeat protein 5 (FBXL5)-mediated degradation, ALKBH5 overexpression incurred a significant reduction in iron-regulatory protein IRP2 and the modulator of epithelial-mesenchymal transition (EMT) SNAI1. ALKBH5 in protecting against PDAC through modulating regulators of iron metabolism and underscore the multifaceted role of m6A in pancreatic cancer.

Forkhead box protein M1 (FOXM1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	HaCAT cell line	Homo sapiens
Treatment: siALKBH5 HaCAT cells Control: siControl HaCAT cells		GSE211076
Regulation		logFC: 1.11E+00 p-value: 1.78E-33
More Results	Click to View More RNA-seq Results

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[14]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Target Regulation	Up regulation
Pathway Response	Glioma			hsa05214
Cell Process	Cells proliferation
Cell Process	Signaling pathways regulating pluripotency of stem cells (hsa04550)
In-vitro Model	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	Hs 683	Oligodendroglioma	Homo sapiens	CVCL_0844
	SW1783	Anaplastic astrocytoma	Homo sapiens	CVCL_1722
	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
In-vivo Model	For the animal survival analysis, mice were intracranially injected with 10,000 GSCs and maintained until moribund or 80 days after injection. For the rescue studies, GSCs with ALKBH5 or FOXM1-AS shRNAs were co-transfected with a FOXM1, ALKBH5 wild-type or mutant expression construct.
Response Summary	ALKBH5 and FOXM1-AS disrupted GSC tumorigenesis through the Forkhead box protein M1 (FOXM1) axis.

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[15]
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulation	Up regulation
Pathway Response	Cellular senescence			hsa04218
Cell Process	Cell proliferation and invasion
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vitro Model	NCI-H522	Lung adenocarcinoma	Homo sapiens	CVCL_1567
In-vivo Model	1 × 10⁷ A549 cells were subcutaneously implanted into 4-week-old NOD/SCID mice.
Response Summary	m6A demethylase ALKBH5 affects the proliferation and invasion of lung adenocarcinoma cells under IH by downregulating m6A modification on Forkhead box protein M1 (FOXM1) mRNA and by promoting FOXM1 expression.high FOXM1 expression was associated with cisplatin-based chemotherapy resistance and poor prognosis

Melanoma of uvea [ICD-11: 2D0Y]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[16]
Responsed Disease	Melanoma of uvea [ICD-11: 2D0Y]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	ARPE-19	Normal	Homo sapiens	CVCL_0145
	C918	Uveal melanoma	Homo sapiens	CVCL_8471
	MuM-2B	Uveal melanoma	Homo sapiens	CVCL_3447
In-vivo Model	The in vivo experiment method for transplantation of tumors was subcutaneous injection of 1 × 10⁷ ALKBH5-stable knockdown C918 cells into BALB/c nude mice.
Response Summary	AKLBH5-induced m6A demethylation of Forkhead box protein M1 (FOXM1) mRNA promotes uveal melanoma progression.

Idiopathic interstitial pneumonitis [ICD-11: CB03]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[17]
Responsed Disease	Pulmonary Fibrosis [ICD-11: CB03.4]
Target Regulation	Up regulation
In-vitro Model	NIH 3T3	Normal	Mus musculus	CVCL_0594
In-vitro Model	MRC-5	Normal	Homo sapiens	CVCL_0440
In-vivo Model	For the mouse model of miR-320a-3p overexpression, a total of 24 male C57BL/6 mice were divided randomly into four groups (n = 6 in each group): saline, silica, silica plus AAV9-miR-NC, and silica plus AAV9-miR-320a-3p. The mice in the silica plus AAV9-miR-NC/AAV9-miR-320a-3p groups were anesthetized using the same method, then administered intratracheally 50 uL AAV9-miR-NC/AAV9-miR-320a-3p per mouse at a titer of 8 × 10¹² v. g./ml. Three weeks later, these mice were treated in the same way using anesthesia, saline, and silica as mentioned above. Subsequently, after 4 weeks, the mice were sacrificed, and the lungs were isolated and frozen at -80 ℃ for further study.
Response Summary	ALKBH5 promotes silica-induced lung fibrosis via the miR-320a-3p/FOXM1 axis or targeting Forkhead box protein M1 (FOXM1) directly.

Forkhead box protein O3 (FOXO3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: -1.05E+00 p-value: 3.53E-06
More Results	Click to View More RNA-seq Results

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[18]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Pathway Response	FoxO signaling pathway			hsa04068
In-vitro Model	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	FHC	Normal	Homo sapiens	CVCL_3688
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
Response Summary	ALKBH5 plays an antitumor role in colorectal cancer by modulating the Forkhead box protein O3 (FOXO3)/miR-21/SPRY2 axis, which not only suggests a regulatory effect between ALKBH5 and FOXO3, but also provides a new therapeutic direction for colorectal cancer.

Cardiomyopathy [ICD-11: BC43]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[19]
Responsed Disease	Diabetic cardiomyopathy [ICD-11: BC43.7]
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway	hsa04390
	FoxO signaling pathway	hsa04068
Cell Process	Cell apoptosis
In-vitro Model	Neonatal rat ventricular cardiomyocytes (Primary myocyte cells)
In-vivo Model	The model mice were intraperitoneally injected with streptozotocin (STZ; Sigma-Aldrich Corp., USA). The dose of STZ was 50 mg/kg for 5 days. 7 days after the last injection, blood glucose concentrations were recorded. Mouse models of diabetes were considered established when fasting blood glucose concentrations reached >11.1 mmol/L, and body weight was measured.
Response Summary	ALKBH5 was upregulated in the cardiomyocytes of diabetic cardiomyopathy mice and posttranscriptionally activated Forkhead box protein O3 (FOXO3) by m6A demethylation in an m6A-YTHDF2-dependent manner.This work reveals the key function of the ALKBH5-FOXO3-CDR1as/Hippo signaling pathway in DCM and provides insight into the critical roles of m6A methylation in DCM.

High mobility group protein B1 (HMGB1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	MOLM-13 cell line	Homo sapiens
Treatment: shALKBH5 MOLM-13 cells Control: shNS MOLM-13 cells		GSE144968
Regulation		logFC: -2.13E+00 p-value: 2.89E-03
More Results	Click to View More RNA-seq Results

Liver disease [ICD-11: DB9Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[20]
Responsed Disease	Liver disease [ICD-11: DB9Z]
Target Regulation	Down regulation
Cell Process	Immune Response
	Cell apoptosis
Response Summary	ALKBH5-dependent High mobility group protein B1 (HMGB1) expression mediates STING-interferon regulatory factor 3 innate immune response in radiation-induced liver diseases.

Insulin-like growth factor 1 receptor (IGF1R)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	MOLM-13 cell line	Homo sapiens
Treatment: shALKBH5 MOLM-13 cells Control: shNS MOLM-13 cells		GSE144968
Regulation		logFC: -6.16E-01 p-value: 4.93E-02
More Results	Click to View More RNA-seq Results

Endometrial cancer [ICD-11: 2C76]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[21]
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulation	Up regulation
In-vitro Model	T HESCs	Normal	Homo sapiens	CVCL_C464
	RL95-2	Endometrial adenosquamous carcinoma	Homo sapiens	CVCL_0505
	HEC-1-A	Endometrial adenocarcinoma	Homo sapiens	CVCL_0293
Response Summary	ALKBH5 promoted proliferation and invasion of endometrial cancer via erasing Insulin-like growth factor 1 receptor (IGF1R) m6A-modifications

Interferon beta (IFNB1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	Peritoneal macrophages	Mus musculus
Treatment: ALKBH5-/- peritoneal macrophages Control: Wild type peritoneal macrophages		GSE127739
Regulation		logFC: -6.45E-01 p-value: 8.14E-03
More Results	Click to View More RNA-seq Results

Cytomegaloviral disease [ICD-11: 1DB2]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[22]
Responsed Disease	Unspecified viral infection [ICD-11: 1D9Z]
Target Regulation	Up regulation
Pathway Response	Cellular senescence			hsa04218
Cell Process	Metabolic reprogramming
	Stress responses
	Aging
In-vitro Model	BSC40	Normal	Chlorocebus pygerythrus	CVCL_3656
	HCMV AD169GFP (Human cytomegalovirus)
	NHDF (Primary Normal Human Dermal Fibroblasts)
	Vero	Normal	Chlorocebus sabaeus	CVCL_0059
Response Summary	Responses to nonmicrobial dsDNA in uninfected cells, which shape host immunity and contribute to autoimmune disease, are regulated by enzymes controlling m6A epitranscriptomic changes. While METTL14 depletion reduced virus reproduction and stimulated dsDNA- or HCMV-induced Interferon beta (IFNB1) mRNA accumulation, ALKBH5 depletion had the opposite effect.

Innate immunity [ICD-11: 4A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[22]
Responsed Disease	Innate immunity [ICD-11: 4A00]
Target Regulation	Up regulation
Pathway Response	Cellular senescence			hsa04218
Cell Process	Metabolic reprogramming
	Stress responses
	Aging
In-vitro Model	BSC40	Normal	Chlorocebus pygerythrus	CVCL_3656
	HCMV AD169GFP (Human cytomegalovirus)
	NHDF (Primary Normal Human Dermal Fibroblasts)
	Vero	Normal	Chlorocebus sabaeus	CVCL_0059
Response Summary	Responses to nonmicrobial dsDNA in uninfected cells, which shape host immunity and contribute to autoimmune disease, are regulated by enzymes controlling m6A epitranscriptomic changes. While METTL14 depletion reduced virus reproduction and stimulated dsDNA- or HCMV-induced Interferon beta (IFNB1) mRNA accumulation, ALKBH5 depletion had the opposite effect.

Ly6/PLAUR domain-containing protein 1 (LYPD1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: 7.22E-01 p-value: 3.53E-02
More Results	Click to View More RNA-seq Results

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[23]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Down regulation
In-vitro Model	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	BEL-7402	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492
Response Summary	ALKBH5 suppressed the proliferation and invasion capabilities of HCC cells in vitro and in vivo. Mechanistically, ALKBH5-mediated m6A demethylation led to a post-transcriptional inhibition of Ly6/PLAUR domain-containing protein 1 (LYPD1).

Metalloproteinase inhibitor 3 (TIMP3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	HaCAT cell line	Homo sapiens
Treatment: siALKBH5 HaCAT cells Control: siControl HaCAT cells		GSE211076
Regulation		logFC: -5.86E-01 p-value: 2.60E-20
More Results	Click to View More RNA-seq Results

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[24]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Down regulation
Cell Process	RNA stability
Cell Process	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	NHBE (Normal bronchial epithelial cells)
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630
In-vivo Model	2 × 10⁶ A549 cells stably transfected with shRNA-ALKBH5 were injected into the flank of male athymic BALB/c nude mice (4-5 weeks old, 10 mice).
Response Summary	ALKBH5 repress Metalloproteinase inhibitor 3 (TIMP3) transcript stability, thereby inhibiting TIMP3 translational production.the present research confirmed the ALKBH5/TIMP3 pathway in the non-small cell lung cancer(NSCLC) oncogenesis progress, providing a novel insight for the epitranscriptome and potential therapeutic target for NSCLC.

Mothers against decapentaplegic homolog 3 (SMAD3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	MOLM-13 cell line	Homo sapiens
Treatment: shALKBH5 MOLM-13 cells Control: shNS MOLM-13 cells		GSE144968
Regulation		logFC: 1.59E+00 p-value: 2.50E-03
More Results	Click to View More RNA-seq Results

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[25]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Down regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	The mice were divided into control group and ALKBH5-overexpressing group (9 mice per group). ALKBH5-overexpressing and control A549 cells (3 × 10⁶ cells/mouse) in 200 uL PBS were intravenously (i.v.) injected into the lateral tail vein of mice. At every 5th day post-inoculation, TGF-Beta-1 (4 ug/kg body weight) was intraperitoneally (i.p.) injected to promote tumor cell metastasis. Eight weeks later, the mice were euthanized, and then their lungs and livers were taken out and fixed in Bouin's solution (Sigma Aldrich, HT101128) or 4% Paraformaldehyde (Beyotime, p0099, Shanghai, China) for macroscopically metastatic nodule analysis.
Response Summary	ALKBH5 weakens YTHDF1/3-mediated TGF-Beta-R2 and Mothers against decapentaplegic homolog 3 (SMAD3) mRNA stabilization, and abolishes YTHDF2-mediated SMAD6 mRNA degradation, supporting the notion that ALKBH5 inhibits TGF-Beta-induced EMT and invasion of NSCLC cells via YTHD1/2/3-mediated mechanism.

Mothers against decapentaplegic homolog 6 (SMAD6)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	THP1 cell line	Homo sapiens
Treatment: ALKBH5 knockdown THP1 cells Control: Wild type THP1 cells		GSE128574
Regulation		logFC: 7.02E-01 p-value: 2.75E-03
More Results	Click to View More RNA-seq Results

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[25]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Up regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	The mice were divided into control group and ALKBH5-overexpressing group (9 mice per group). ALKBH5-overexpressing and control A549 cells (3 × 10⁶ cells/mouse) in 200 uL PBS were intravenously (i.v.) injected into the lateral tail vein of mice. At every 5th day post-inoculation, TGF-Beta-1 (4 ug/kg body weight) was intraperitoneally (i.p.) injected to promote tumor cell metastasis. Eight weeks later, the mice were euthanized, and then their lungs and livers were taken out and fixed in Bouin's solution (Sigma Aldrich, HT101128) or 4% Paraformaldehyde (Beyotime, p0099, Shanghai, China) for macroscopically metastatic nodule analysis.
Response Summary	ALKBH5 weakens YTHDF1/3-mediated TGF-Beta-R2 and SMAD3 mRNA stabilization, and abolishes YTHDF2-mediated Mothers against decapentaplegic homolog 6 (SMAD6) mRNA degradation, supporting the notion that ALKBH5 inhibits TGF-Beta-induced EMT and invasion of NSCLC cells via YTHD1/2/3-mediated mechanism.

Mutated in multiple advanced cancers 1 (PTEN)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	MOLM-13 cell line	Homo sapiens
Treatment: shALKBH5 MOLM-13 cells Control: shNS MOLM-13 cells		GSE144968
Regulation		logFC: -2.10E+00 p-value: 1.89E-02
More Results	Click to View More RNA-seq Results

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[26]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Pathway Response	.PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation
	Cell migration
	Epithelial-mesenchymal transition
	Cell apoptosis
In-vitro Model	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	CFPAC-1	Cystic fibrosis	Homo sapiens	CVCL_1119
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
Response Summary	ALKBH5-mediated m6A demethylation enhanced the stability of KCNK15-AS1. In pancreatic cancer, KCNK15-AS1 bound to KCNK15 to inhibit its translation, and interacted with MDM2 to induce REST ubiquitination, which eventually facilitated Mutated in multiple advanced cancers 1 (PTEN) transcription to inactivate AKT pathway.

Myeloid differentiation primary response protein MyD88 (MYD88)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: 9.11E-01 p-value: 2.76E-05
More Results	Click to View More RNA-seq Results

Skeletal anomaly [ICD-11: LD24]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[27]
Responsed Disease	Skeletal anomaly [ICD-11: LD24]
Target Regulation	Down regulation
Pathway Response	Central carbon metabolism in cancer	hsa05230
Cell Process	Glucose metabolism
In-vitro Model	Mesenchymal stem cell line (NP tissues were used to isolate NP cells)
Response Summary	METTL3 positively regulates expression of Myeloid differentiation primary response protein MyD88 (MYD88), a critical upstream regulator of NF-Kappa-B signaling, by facilitating m6A methylation modification to MYD88-RNA, subsequently inducing the activation of NF-Kappa-B which is widely regarded as a repressor of osteogenesis and therefore suppressing osteogenic progression. The METTL3-mediated m6A methylation is found to be dynamically reversed by the demethylase ALKBH5.

Myt1 kinase (PKMYT1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	HaCAT cell line	Homo sapiens
Treatment: siALKBH5 HaCAT cells Control: siControl HaCAT cells		GSE211076
Regulation		logFC: 1.57E+00 p-value: 1.28E-17
More Results	Click to View More RNA-seq Results

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[28]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Down regulation
Cell Process	Cell invasion
	Cell migration
In-vitro Model	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
In-vivo Model	After randomly assignment and anesthetization, nude mice were injected with 5 × 10⁶ cells suspended in 100 uL PBS into the tail vein (n = 5 per group).
Response Summary	Myt1 kinase (PKMYT1), as a downstream target of ALKBH5, promoted invasion and migration in GC. Moreover IGF2BP3 helped stabilize the mRNA stability of PKMYT1 via its m6A modification site.

Paired mesoderm homeobox protein 1 (PRRX1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: -9.92E-01 p-value: 2.75E-02
More Results	Click to View More RNA-seq Results

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[29]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Up regulation
Pathway Response	p53 signaling pathway			hsa04115
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	Cells at 1 × 10⁶ were subcutaneously injected into the mice similarly to nude mice. Twenty-eight days later, grafted tumors were collected and morphologically analyzed.
Response Summary	Knockdown of p53 or inhibition of p53's transcriptional activity by addition of its specific inhibitor PFT-Alpha decreased expression of ALKBH5 and Cancer stem cells' malignancies, the pivotal role of ALKBH5 in Cancer stem cells derived from nonsmall-cell lung cancer and highlight the regulatory function of the p53/ALKBH5 axis in modulating CSC progression. p53 transcriptionally regulates Paired mesoderm homeobox protein 1 (PRRX1), which is consistent with our previous report.

Period circadian protein homolog 1 (PER1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	NOMO-1 cell line	Homo sapiens
Treatment: shALKBH5 NOMO-1 cells Control: shNS NOMO-1 cells		GSE144968
Regulation		logFC: 1.46E+00 p-value: 8.91E-04
More Results	Click to View More RNA-seq Results

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[30]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Target Regulation	Up regulation
Pathway Response	p53 signaling pathway			hsa04115
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	CFPAC-1	Cystic fibrosis	Homo sapiens	CVCL_1119
	HPDE6c7	Normal	Homo sapiens	CVCL_0P38
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	SW1990	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1723
Response Summary	ALKBH5 serves as a pancreatic cancer suppressor by regulating the posttranscriptional activation of Period circadian protein homolog 1 (PER1) through m6A abolishment, which highlights a demethylation-based approach for PC diagnosis and therapy. ALKBH5 loss downregulated PER1 mRNA levels in an m6A-YTHDF2-dependent manner.

PI3-kinase subunit alpha (PI3k/PIK3CA)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	MOLM-13 cell line	Homo sapiens
Treatment: shALKBH5 MOLM-13 cells Control: shNS MOLM-13 cells		GSE144968
Regulation		logFC: -2.12E+00 p-value: 2.82E-03
More Results	Click to View More RNA-seq Results

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[2]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
In-vitro Model	A2780	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	CoC1	Ovarian adenocarcinoma	Homo sapiens	CVCL_6891
	OVCAR-3	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0465
	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In-vivo Model	SKOV3 or A2780 cells were infected with the indicated lentiviral vectors and injected (5 × 10⁶ cells/mouse in 200 uL volume) subcutaneously into the left armpit of 6-week-old BALB/c nude mice. After 21 days, the animals were sacrificed to confirm the presence of tumors and weigh the established tumors
Response Summary	ALKBH5 is a tumor-promoting gene in epithelial ovarian cancer, which is involved in the mTOR pathway and BCL-2-Beclin1 complex. ALKBH5 activated EGFR-PI3-kinase subunit alpha (PI3k/PIK3CA)-AKT-mTOR signaling pathway. ALKBH5 inhibited autophagy of epithelial ovarian cancer through miR-7 and BCL-2.

Programmed cell death 1 ligand 1 (CD274/PD-L1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: 2.95E+00 p-value: 3.40E-21
More Results	Click to View More RNA-seq Results

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[31]
Responsed Disease	Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10]
Target Regulation	Up regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
In-vitro Model	TFK-1	Cholangiocarcinoma	Homo sapiens	CVCL_2214
	RBE	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_4896
	LIPF178c (LIPF178c human bile duct cancer cells from China Center for Type Culture Collection (Wuhan, China))
	LIPF155c (LIPF155c human bile duct cancer cells from China Center for Type Culture Collection (Wuhan, China))
	LICCF (LICCF human intrahepatic bile duct cancer cell line from China Center for Type Culture Collection (Wuhan, China))
	HCCC-9810	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_6908
In-vivo Model	ICC tumor cells (LIPF178c-shCtrl/shALKBH5) of 5 × 10⁶ were injected into the right flank of NCG mice. Tumor volume was calculated by the formula: volume = ab2/2 (a, the longer axis; b, the shorter axis). T-cell killing assay in vitro was conducted as previously reported (20). PBMCs from healthy donors were activated and expanded as described above. The day before tumor cell injection, PBMC (i.v. 1 × 10⁷ cells) was adoptively transferred to NCG mice via the tail vein. At the end, the PBMC was isolated and subjected to flow cytometry for detecting T-cell percentage.
Response Summary	ALKBH5 as an important m6A demethylase that orchestrates Programmed cell death 1 ligand 1 (CD274/PD-L1) expression in intrahepatic cholangiocarcinoma (ICC).

Protein patched homolog 1 (PTCH1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: -7.48E-01 p-value: 6.04E-03
More Results	Click to View More RNA-seq Results

Hepatic fibrosis/cirrhosis [ICD-11: DB93]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[32]
Responsed Disease	Hepatic fibrosis [ICD-11: DB93.0]
Target Regulation	Up regulation
Pathway Response	Hedgehog signaling pathway	hsa04340
In-vitro Model	HSCs (Hepatic stellate cells(HSCs) were purchased from American Type Culture Collections (Manassas, VA))
In-vivo Model	Liver fibrosis mice model was induced by intraperitoneal CCl₄ injection for 12 weeks. The dose regimen for CCl₄ in mice is 1 ml kg^-1, diluted to 50% with olive oil twice per week for 12 weeks. Until 11 weeks, mice with liver-specific disruption of ALKBH5 were given hydrodynamic tail-vein injections of LV5-ALKBH5.
Response Summary	ALKBH5 mediated Protein patched homolog 1 (PTCH1) activation via a m6A-dependent manner,ALKBH5 ameliorated liver fibrosis and suppressed HSCs activation via triggering PTCH1 activation in a m6A dependent manner.

Protein phosphatase 1A (PPM1A)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	MOLM-13 cell line	Homo sapiens
Treatment: shALKBH5 MOLM-13 cells Control: shNS MOLM-13 cells		GSE144968
Regulation		logFC: -9.55E-01 p-value: 2.96E-02
More Results	Click to View More RNA-seq Results

Male infertility [ICD-11: GB04]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[33]
Responsed Disease	Azoospermia [ICD-11: GB04.0]
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	RNA stability
	Cell autophagy
In-vitro Model	TM3	Normal	Mus musculus	CVCL_4326
In-vivo Model	Male SPF BALB/c mice (qls02-0202) were purchased from Qinglongshan animal breeding farm. Mice were sacrificed by CO₂ asphyxiation and testes were obtained for following histopathological analyses.
Response Summary	m6A modification promoted translation of Protein phosphatase 1A (PPM1A) (protein phosphatase 1A, magnesium dependent, alpha isoform), a negative AMP-activated protein kinase (AMPK) regulator, but decreased expression of CAMKK2 (calcium/calmodulin-dependent protein kinase kinase 2, beta), a positive AMPK regulator, by reducing its RNA stability. Similar regulation of METTL14, ALKBH5, and m6A was also observed in LCs upon treatment with human chorionic gonadotropin (HsCG). Knock down of YTHDF1 failed to change the expression of CAMKK2 Providing insight into novel therapeutic strategies by exploiting m6A RNA methylation as targets for treating azoospermatism and oligospermatism patients with reduction in serum testosterone.

Protein salvador homolog 1 (SAV1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: -1.29E+00 p-value: 1.15E-10
More Results	Click to View More RNA-seq Results

Multiple myeloma [ICD-11: 2A83]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[34]
Responsed Disease	Multiple myeloma [ICD-11: 2A83.1]
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Cell proliferation
	Cell invasion
In-vitro Model	U266 (Human multiple myeloma cells)
	RPMI-8226	Plasma cell myeloma	Homo sapiens	CVCL_0014
	NCI-H929	Plasma cell myeloma	Homo sapiens	CVCL_1600
	ARH-77	Human leukemia tumor	Homo sapiens	CVCL_1072
Response Summary	Inhibiting ALKBH5 in Multiple Myeloma cells increased Protein salvador homolog 1 (SAV1) m6A levels, decreased SAV1 mRNA stability and expression, suppressed the stem cell related HIPPO-pathway signalling and ultimately activates the downstream effector YAP, exerting an anti-myeloma effect.

Protein sprouty homolog 2 (SPRY2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	NOMO-1 cell line	Homo sapiens
Treatment: shALKBH5 NOMO-1 cells Control: shNS NOMO-1 cells		GSE144968
Regulation		logFC: -2.18E+00 p-value: 1.77E-03
More Results	Click to View More RNA-seq Results

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[18]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway			hsa04068
In-vitro Model	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	FHC	Normal	Homo sapiens	CVCL_3688
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
Response Summary	ALKBH5 plays an antitumor role in colorectal cancer by modulating the FOXO3/miR-21/Protein sprouty homolog 2 (SPRY2) axis, which not only suggests a regulatory effect between ALKBH5 and FOXO3, but also provides a new therapeutic direction for colorectal cancer.

Protein Wnt-5a (WNT5A)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	CAG cell line	Homo sapiens
Treatment: shALKBH5 CAG cells Control: shNC CAG cells		GSE180214
Regulation		logFC: -9.66E-01 p-value: 2.63E-04
More Results	Click to View More RNA-seq Results

Diseases of the circulatory system [ICD-11: BE2Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[35]
Responsed Disease	Diseases of the circulatory system [ICD-11: BE2Z]
Target Regulation	Down regulation
In-vitro Model	CMECs (Cardiac Microvascular Endothelial Cells )
Response Summary	ALKBH5 is a negative regulator of post-ischemic angiogenesis via post-transcriptional modulation and destabilization of Protein Wnt-5a (WNT5A) mRNA in an m6A-dependent manner.

RAC-alpha serine/threonine-protein kinase (AKT1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: -9.73E-01 p-value: 3.10E-07
More Results	Click to View More RNA-seq Results

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[26]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Pathway Response	Apoptosis			hsa04210
	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation
	Cell migration
	Epithelial-mesenchymal transition
	Cell apoptosis
In-vitro Model	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	CFPAC-1	Cystic fibrosis	Homo sapiens	CVCL_1119
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
Response Summary	ALKBH5-mediated m6A demethylation enhanced the stability of KCNK15-AS1. In pancreatic cancer, KCNK15-AS1 bound to KCNK15 to inhibit its translation, and interacted with MDM2 to induce REST ubiquitination, which eventually facilitated PTEN transcription to inactivate RAC-alpha serine/threonine-protein kinase (AKT1) pathway.

Ossification of spinal ligaments [ICD-11: FA83]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[4]
Responsed Disease	Ossification of spinal ligaments [ICD-11: FA83]
Responsed Drug	MK22606	Investigative	Drug Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway		hsa04151
Cell Process	Ossification
In-vitro Model	Ligamentum flavum cells (Ligamentum flavum cells)
Response Summary	The overexpression of ALKBH5 led to the activation of RAC-alpha serine/threonine-protein kinase (AKT1), and BMP2 was regulated by ALKBH5 through the AKT signaling pathway. ALKBH5 promoted the osteogenesis of the ligamentum flavum cells through BMP2 demethylation and AKT activation. MK22606 is an AKT inhibitor. Moreover, when ALKBH5 was knocked down in the ligamentum flavum cells, p-AKT was inhibited when compared with that in the overexpressed ALKBH5 and control groups.

RIG-I-like receptor 1 (RIG-I)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	Cal27 cell line	Homo sapiens
Treatment: siALKBH5 Cal27 cells Control: siScramble Cal27 cells		GSE185886
Regulation		logFC: 7.29E-01 p-value: 2.91E-02
More Results	Click to View More RNA-seq Results

Head and neck squamous carcinoma [ICD-11: 2B6E]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[36]
Responsed Disease	Head and neck squamous carcinoma [ICD-11: 2B6E]
Target Regulation	Down regulation
Pathway Response	RIG-I-like receptor signaling pathway			hsa04622
In-vitro Model	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107
	SCC-4	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1684
	SCC-25	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1682
	HEK293T	Normal	Homo sapiens	CVCL_0063
	()
In-vivo Model	For the subcutaneous implantation model, 1 × 10⁶ Cal27 cells stably transduced with lentivirus were injected into the left or right flanks of BALB/c nude mice (aged 4-6 weeks). Following stable transfection, 2 × 10⁵ SCC7 cells were subcutaneously inoculated into C3H mice (aged 6-8 weeks).
Response Summary	ALKBH5 overexpression inhibits RIG-I-mediated IFN-Alpha secretion through the IKK-Epsilon/TBK1/IRF3 pathway. Upregulation of AKLBH5 negatively correlates with RIG-I-like receptor 1 (RIG-I) and IFN-Alpha expression in head and neck squamous cell carcinoma (HNSCC) patients.

Runt-related transcription factor 2 (Runx2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	CAG cell line	Homo sapiens
Treatment: shALKBH5 CAG cells Control: shNC CAG cells		GSE180214
Regulation		logFC: 7.14E-01 p-value: 3.96E-04
More Results	Click to View More RNA-seq Results

Diseases of the musculoskeletal system [ICD-11: FC0Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[37]
Responsed Disease	Diseases of the musculoskeletal system [ICD-11: FC0Z]
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway	hsa03015
	RNA degradation	hsa03018
Cell Process	RNA stability
Response Summary	ALKBH5 promotes osteogenesis through modulating Runt-related transcription factor 2 (Runx2) mRNA stability.

Scavenger receptor class F member 1 (SCARF1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	NOMO-1 cell line	Homo sapiens
Treatment: shALKBH5 NOMO-1 cells Control: shNS NOMO-1 cells		GSE144968
Regulation		logFC: 5.88E-01 p-value: 6.33E-03
More Results	Click to View More RNA-seq Results

Acute myocardial infarction [ICD-11: BA41]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[38]
Responsed Disease	Acute myocardial infarction [ICD-11: BA41]
Cell Process	Lysosomal escape
In-vivo Model	Wild-type C57 (female, 12-16 weeks old), ALKBH5 /- mice (female and male, 12-16 weeks old), and SPF-grade SD rats (female, 180-230 g) were used to establish the AMI model.Sodium pentobarbital diluted to 10 mg/mL was used to anesthetize the mice or rat at the dose of 50 mg/kg through an intraperitoneal injection. By using a small animal ventilator with endotracheal intubation, thoracotomy was performed at the left fourth intercostal region. The heart was exposed, and the left anterior descending coronary artery (LCA) was occluded through a 6-0 silk suture that was placed 2-3 mm distal to the origin of the LCA with a slipknot. The apical region turned white, and ST segment elevation and T wave inversion of ECG showed that the AMI model was successfully established. Forty-five minutes after ischemia, the slipknot was released, and the ischemic region was reperfused. PBS (0.2 ml), HSSS (23.5 mg/kg, 0.2 ml), IOX1 (10 mg/kg, 0.2 ml), and HSSS-I (33.5 mg/kg, containing 10 mg/kg IOX1, 0.2 ml) were administered through caudal vein injection for 14 days at the frequency of one time per day.
Response Summary	IOX1, which is an inhibitor of ALKBH5, was loaded on HSSS to form HSSS-I, which could effectively ameliorate cardiac dysfunction in acute myocardial infarction. The surface-modified bioengineered ferritin nanocage targeted the dying cells in the infarct area under the guidance of Scavenger receptor class F member 1 (SCARF1). These cells were then phagocytosed through recognition of their TfR1 receptor.

Serine/threonine-protein kinase LATS2 (LATS2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	CAG cell line	Homo sapiens
Treatment: shALKBH5 CAG cells Control: shNC CAG cells		GSE180214
Regulation		logFC: 7.85E-01 p-value: 1.18E-03
More Results	Click to View More RNA-seq Results

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[39]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Cell Process	Cell proliferation
	Cell invasion
	Cell migration
	Cell EMT
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	For the experiments, mice were injected with 5 × 10⁶ lung cancer cells with stably expression of relevant plasmids and randomly divided into indicated groups (five mice per group). To assess the in vivo effects of cycloleucine, the xenografted tumors had reached approximately 5 mm in diameter from mice and then these xenografted mice were feed with Vehicle or cycloleucine (25 mg/kg twice weekly) and tumor volume were measured every 3 day. Tumor volume was estimated as 0.5 × a² × b (where a and b represent a tumors short and long diameter, respectively). Mice were euthanized after 7 weeks and the tumors were measured a final time.
Response Summary	m6A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/Serine/threonine-protein kinase LATS2 (LATS2)-mediated YAP activity in non-small cell lung cancer.

Serine/threonine-protein kinase STK11 (STK11/LKB1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: 6.73E-01 p-value: 8.05E-04
More Results	Click to View More RNA-seq Results

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[40]
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulation	Down regulation
In-vitro Model	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	MRC-9	Normal	Homo sapiens	CVCL_2629
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	H1795 (Lung cancer H1795 cell lines were purchased from ATCC, USA)
	NCI-H1792	Lung adenocarcinoma	Homo sapiens	CVCL_1495
	NCI-H1703	Lung squamous cell carcinoma	Homo sapiens	CVCL_1490
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
Response Summary	ALKBH5 gain- or loss-of function could effectively reverse Serine/threonine-protein kinase STK11 (STK11/LKB1) regulated cell proliferation, colony formation, and migration of KRAS-mutated lung cancer cells.

Signal transducer and activator of transcription 3 (STAT3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: 1.23E+00 p-value: 2.84E-10
More Results	Click to View More RNA-seq Results

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[41]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Down regulation
Pathway Response	JAK-STAT signaling pathway			hsa04630
In-vitro Model	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
	OS3 [Human osteosarcoma]	Osteosarcoma	Homo sapiens	CVCL_F866
	OS2 [Human osteosarcoma]	Osteosarcoma	Homo sapiens	CVCL_F865
	OS1 [Human osteosarcoma]	Osteosarcoma	Homo sapiens	CVCL_F864
	KHOS/NP	Osteosarcoma	Homo sapiens	CVCL_2546
Response Summary	ALKBH5 inactivated Signal transducer and activator of transcription 3 (STAT3) pathway by increasing SOCS3 expression via an m6A-YTHDF2-dependent manner. Reducing m6A mRNA levels in human osteosarcoma cells through ALKBH5 up-regulation lead to cell proliferation inhibition, cell apoptosis and cycle arrest.

Sphingosine kinase 1 (SPHK1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: 1.71E+00 p-value: 1.04E-14
More Results	Click to View More RNA-seq Results

Diseases of the circulatory system [ICD-11: BE2Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[42]
Responsed Disease	Diseases of the circulatory system [ICD-11: BE2Z]
Target Regulation	Up regulation
Pathway Response	Vascular smooth muscle contraction			hsa04270
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	HMVE (human microvascular endothelial cells (HMVE) were obtained from ATCC (ATCC-CRL1730))
Response Summary	The study aimed to find the role of m6A RNA demethylase alkB homolog 5 (ALKBH5) in ECs angiogenesis during ischemic injury. ALKBH5 helps in the maintenance of angiogenesis in endothelial cells following acute ischemic stress via reduced SPHK1 m6A methylation and downstream eNOS-AKT signaling.

Stimulator of interferon genes protein (STING1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	CAG cell line	Homo sapiens
Treatment: shALKBH5 CAG cells Control: shNC CAG cells		GSE180214
Regulation		logFC: 6.04E-01 p-value: 6.54E-03
More Results	Click to View More RNA-seq Results

Liver disease [ICD-11: DB9Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[20]
Responsed Disease	Liver disease [ICD-11: DB9Z]
Target Regulation	Down regulation
Cell Process	Immune Response
	Cell apoptosis
Response Summary	ALKBH5-dependent HMGB1 expression mediates Stimulator of interferon genes protein (STING1)-interferon regulatory factor 3 innate immune response in radiation-induced liver diseases.

SUMO specific peptidase 1 (SENP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	NOMO-1 cell line	Homo sapiens
Treatment: shALKBH5 NOMO-1 cells Control: shNS NOMO-1 cells		GSE144968
Regulation		logFC: -8.95E-01 p-value: 1.12E-02
More Results	Click to View More RNA-seq Results

Diseases of the circulatory system [ICD-11: BE2Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[43]
Responsed Disease	Diseases of the circulatory system [ICD-11: BE2Z]
Target Regulation	Down regulation
Pathway Response	Apoptosis			hsa04210
	Chemical carcinogenesis - reactive oxygen species			hsa05208
Cell Process	Oxygen species(ROS)-induced stress
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	For the ROS-induced DNA damage analysis, the indicated cell lines were treated with or without 100 uM hydrogen peroxide (H₂O₂), or 80 uM Carbonyl cyanide m-chlorophenylhydrazone (CCCP) for 6 hours. For the in vivo ROS study, DMSO and 5 mg/kg CCCP was intraperitoneally injected in to three pairs of mice.
Response Summary	ROS promotes ALKBH5 SUMOylation through activating ERK/EPHB2/JNK signaling, leading to inhibition of ALKBH5 m6A demethylase activity by blocking substrate accessibility. Post-translational modification of ALKBH5 regulates ROS-induced DNA damage response. ROS specifically promotes ALKBH5 but not FTO, METTL3 and METTL14 SUMOylation by enhancing the interaction of ALKBH5 and UBC9 and inhibiting the association between ALKBH5 and SUMO specific peptidase 1 (SENP1).

Suppressor of cytokine signaling 3 (SOCS3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	RPMI-8226 cell line	Homo sapiens
Treatment: shALKBH5 RPMI8226 cells Control: shNC RPMI8226 cells		GSE180214
Regulation		logFC: -7.50E-01 p-value: 1.38E-03
More Results	Click to View More RNA-seq Results

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[41]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Down regulation
Pathway Response	JAK-STAT signaling pathway			hsa04630
In-vitro Model	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
	OS3 [Human osteosarcoma]	Osteosarcoma	Homo sapiens	CVCL_F866
	OS2 [Human osteosarcoma]	Osteosarcoma	Homo sapiens	CVCL_F865
	OS1 [Human osteosarcoma]	Osteosarcoma	Homo sapiens	CVCL_F864
	KHOS/NP	Osteosarcoma	Homo sapiens	CVCL_2546
Response Summary	ALKBH5 inactivated STAT3 pathway by increasing Suppressor of cytokine signaling 3 (SOCS3) expression via an m6A-YTHDF2-dependent manner. Reducing m6A mRNA levels in human osteosarcoma cells through ALKBH5 up-regulation lead to cell proliferation inhibition, cell apoptosis and cycle arrest.

Target of rapamycin complex subunit LST8 (MLST8)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	NOMO-1 cell line	Homo sapiens
Treatment: shALKBH5 NOMO-1 cells Control: shNS NOMO-1 cells		GSE144968
Regulation		logFC: -6.36E-01 p-value: 6.23E-04
More Results	Click to View More RNA-seq Results

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[12]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	HL-60	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	HL-60 cells (1 × 10⁷) suspended in 0.1 ml PBS containing 50% Matrigel were subcutaneously injected into the flanks of the mice. When tumor sizes reached 200 mm³, the mice were randomly distributed into four groups with the indicated dosages of saline, cytarabine and BP alone or in combination. For BP injections, the solution was delivered intraperitoneally at 106 ug/kg body weight for the first 8 consecutive days. For cytarabine injections, the solution was delivered intraperitoneally at 100 mg/kg body weight three times (once every three days). The combination group was administered intraperitoneally three times (once every three days) with the same dosages as described above. The control group was treated with an equivalent amount of saline.
Response Summary	Bioactive peptides can inhibit acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m6A demethylation of EIF4EBP1 and Target of rapamycin complex subunit LST8 (MLST8) mRNAs, which have potential to prevent and treat this disease.

TGF-beta receptor type-2 (TGF-Beta-R2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	NOMO-1 cell line	Homo sapiens
Treatment: shALKBH5 NOMO-1 cells Control: shNS NOMO-1 cells		GSE144968
Regulation		logFC: -1.61E+00 p-value: 9.99E-05
More Results	Click to View More RNA-seq Results

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[25]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Down regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	The mice were divided into control group and ALKBH5-overexpressing group (9 mice per group). ALKBH5-overexpressing and control A549 cells (3 × 10⁶ cells/mouse) in 200 uL PBS were intravenously (i.v.) injected into the lateral tail vein of mice. At every 5th day post-inoculation, TGF-Beta-1 (4 ug/kg body weight) was intraperitoneally (i.p.) injected to promote tumor cell metastasis. Eight weeks later, the mice were euthanized, and then their lungs and livers were taken out and fixed in Bouin's solution (Sigma Aldrich, HT101128) or 4% Paraformaldehyde (Beyotime, p0099, Shanghai, China) for macroscopically metastatic nodule analysis.
Response Summary	ALKBH5 weakens YTHDF1/3-mediated TGF-beta receptor type-2 (TGF-Beta-R2) and SMAD3 mRNA stabilization, and abolishes YTHDF2-mediated SMAD6 mRNA degradation, supporting the notion that ALKBH5 inhibits TGF-Beta-induced EMT and invasion of NSCLC cells via YTHD1/2/3-mediated mechanism.

TNF alpha-induced protein 3 (TNFAIP3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: 1.17E+00 p-value: 2.43E-06
More Results	Click to View More RNA-seq Results

Retinopathy [ICD-11: 9B71]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[44]
Responsed Disease	Diabetic retinopathy [ICD-11: 9B71.0]
Target Regulation	Down regulation
In-vitro Model	BV-2	Normal	Mus musculus	CVCL_0182
In-vivo Model	The male Sprague-Dawley rats (8 weeks old, 200-220 g) were purchased from the Laboratory Animal Center of Sun Yat-sen University. Streptozotocin (Sigma, USA) was given by intraperitoneal injection at a dose of 60 mg/Kg to induce diabetics rats, while the control rats were given by empty citrate buffer. One week after induction, those rats with blood glucose levels > 16.7 mmol/L for three times were considered as successful inducted diabetes. All the rats did not receive insulin during the experiments.In the intraocular injection experiments, rats confirmed as the DM model (blood glucose levels > 16.7 mmol/L for three times) were anesthetized with an intraperitoneal injection of sodium pentobarbital (50 mg/Kg). A total of 10 ul DMEM with 1*10⁹ TU lentiviruses (A20-overexpression, OE-A20 group) or the same volume of DMEM with control lentiviruses (OE-NC group) was injected into the vitreous cavity using a 33-gauge needle. This treatment was performed one time per month, and the rats were sacrificed for further experiments at the 3 months.
Response Summary	Lower expression TNF alpha-induced protein 3 (TNFAIP3) resulted in the enhanced M1 polarization of retinal microglia in diabetic retinopathy, which was caused by ALKBH5 mediated m6A modification.

TNF receptor-associated factor 1 (TRAF1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	RPMI-8226 cell line	Homo sapiens
Treatment: shALKBH5 RPMI8226 cells Control: shNC RPMI8226 cells		GSE180214
Regulation		logFC: -6.91E-01 p-value: 6.11E-06
More Results	Click to View More RNA-seq Results

Multiple myeloma [ICD-11: 2A83]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[45]
Responsed Disease	Multiple myeloma [ICD-11: 2A83.1]
Target Regulation	Up regulation
Pathway Response	MAPK signaling pathway			hsa04010
Cell Process	Cell apoptosis
	RNA stability
In-vitro Model	CAG	Plasma cell myeloma	Homo sapiens	CVCL_D569
	RPMI-8226	Plasma cell myeloma	Homo sapiens	CVCL_0014
	U266 (Human multiple myeloma cells)
In-vivo Model	5 × 10⁵ selected cells were injected via the tail vein into 4- to 5-week-old NCG mice.
Response Summary	ALKBH5 promoted multiple myeloma cell growth and survival through TNF receptor-associated factor 1 (TRAF1)-mediated activation of NF-Kappa-B and MAPK signaling pathways.

TNF receptor-associated factor 4 (TRAF4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: -6.18E-01 p-value: 8.54E-03
More Results	Click to View More RNA-seq Results

Obesity [ICD-11: 5B81]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[46]
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulation	Up regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120), Proteasome
Cell Process	Ubiquitination degradation
In-vitro Model	SVF (Stromal vascular cell fraction (SVF) was isolated from minced inguinal adipose tissue of male C57BL/6J mice (3-4 weeks old))
	3T3-L1	Normal	Mus musculus	CVCL_0123
In-vivo Model	Before the tests, animals were fasted for 8 h. l glucose tolerance test (GTT) was conducted during week 11 on the diet. The mice were challenged with 2 g/kg body weight d-glucose (Sigma-Aldrich, USA). Insulin tolerance test (ITT) was conducted during week 12 on the diet. For insulin tolerance test, mice were injected intraperitoneally with 0.75 U/kg body weight insulin (Sigma-Aldrich, USA). For both tests, blood samples were taken from the tail vein and glucose levels were measured at indicated time points after administration using an AlphaTRAK glucometer
Response Summary	m6A-dependent TNF receptor-associated factor 4 (TRAF4) expression upregulation by ALKBH5 and YTHDF1 contributes to curcumin-induced obesity prevention.

Transcription factor E4F1 (E4F1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: 6.27E-01 p-value: 6.56E-03
More Results	Click to View More RNA-seq Results

Intervertebral disc degeneration [ICD-11: FA80]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[10]
Responsed Disease	Intervertebral disc degeneration [ICD-11: FA80]
Target Regulation	Up regulation
In-vitro Model	Nucleus pulposus cell (The NP tissues were cut into pieces after collection during surgery)
Response Summary	Theses findings reveal an epigenetic interplay mechanism in NPC senescence and IVD degeneration, presenting a critical pro-senescence role of ALKBH5 and m6A hypomethylation, highlighting the therapeutic potential of targeting the m6A/DNMT3B/Transcription factor E4F1 (E4F1) axis for treating IVD degeneration.

Transcription factor EB (TFEB)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	THP1 cell line	Homo sapiens
Treatment: ALKBH5 knockdown THP1 cells Control: Wild type THP1 cells		GSE128574
Regulation		logFC: -1.28E+00 p-value: 2.60E-04
More Results	Click to View More RNA-seq Results

Ischemic heart disease [ICD-11: BA40-BA6Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[47]
Responsed Disease	Ischemic heart disease [ICD-11: BA40-BA6Z]
Target Regulation	Up regulation
Pathway Response	Apoptosis			hsa04210)
Cell Process	Cell proliferation
In-vitro Model	H9c2(2-1)	Normal	Rattus norvegicus	CVCL_0286
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	To cause I/R injury, mice were subjected to 30 min of LAD ischemia followed by 60 min of reperfusion.
Response Summary	METTL3 methylates Transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy genes, at two m6A residues in the 3'-UTR, which promotes the association of the RNA-binding protein HNRNPD with TFEB pre-mRNA and subsequently decreases the expression levels of TFEB. METTL3-ALKBH5 and autophagy, providing insight into the functional importance of the reversible mRNA m6A methylation and its modulators in ischemic heart disease.

Transcription factor SOX-2 (SOX2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	human pluripotent stem cells	Homo sapiens
Treatment: hILO ALKBH5knockout cells Control: hILO wild type cells		GSE163945
Regulation		logFC: -1.63E+00 p-value: 3.34E-04
More Results	Click to View More RNA-seq Results

Endometrial cancer [ICD-11: 2C76]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[48]
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulation	Up regulation
Pathway Response	HIF-1 signaling pathway			hsa04066
	Signaling pathways regulating pluripotency of stem cells			hsa04550
In-vitro Model	EC cell line (Primary EC cells)
	HEC-1-A	Endometrial adenocarcinoma	Homo sapiens	CVCL_0293
	Ishikawa	Endometrial adenocarcinoma	Homo sapiens	CVCL_2529
	RL95-2	Endometrial adenosquamous carcinoma	Homo sapiens	CVCL_0505
In-vivo Model	A method of randomisation was used to determine the experimental groups. In total, 78 female BALB/c nu/nu mice (4-6-week-old) were selected at random and were divided into different groups. A total of 5 × 10⁶ ISK cells or 1 × 10⁴ ECSCisk were suspended in 100 uL of PBS and then were injected into the mice. After 2 weeks, the presence of tumours was examined. ISK cells (5 × 10⁶, 5 × 10⁵, 5 × 10⁴, 1 × 10⁴, or 1 × 10³) and ECSCisk (1 × 10⁴, 1 × 10³, 1 × 10², 10, or 1) were injected and analysed for their abilities to form xenograft tumours. After 4 weeks, subsequent experiments were performed.
Response Summary	HIF-dependent ALKBH5 expression increases in hypoxic TMEs, resulting in the demethylation of Transcription factor SOX-2 (SOX2) mRNA and the maintenance of the Endometrial cancer stem cells phenotype; these data indicate that ECSCs maintain their stemness by activating the HIF/ALKBH5/SOX2 axis under hypoxic conditions.

Transcriptional coactivator YAP1 (YAP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: -6.56E-01 p-value: 3.77E-04
More Results	Click to View More RNA-seq Results

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[49]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Down regulation
Cell Process	Cell growth
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
In-vivo Model	Three-week-old BABL/c female nude mice were randomized into three groups. 5 × 10⁶ 143B cells were subcutaneously injected in mice, and the tumor volume was assessed every 2 weeks. Eight weeks after injection, the animals were killed. The xenograft tumors were harvested and the tumor volumes were calculated by the standard formula: length × width²/2.
Response Summary	ALKBH5 is an anti-tumor factor or a pro-apoptotic factor, acting at least partially by suppressing Transcriptional coactivator YAP1 (YAP1) expression through dual mechanisms with direct m6A methylation of YAP and indirect downregulation of YAP level due to methylation of pre-miR-181b-1. Further results revealed that m6A methylated pre-miR-181b-1 was subsequently recognized by m6A-binding protein YTHDF2 to mediate RNA degradation. However, methylated YAP transcripts were recognized by YTHDF1 to promote its translation. ALKBH5 overexpression was considered a new approach of replacement therapy for osteosarcoma treatment.

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[39]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Cell Process	Cell proliferation
	Cell invasion
	Cell migration
	Cell EMT
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	For the experiments, mice were injected with 5 × 10⁶ lung cancer cells with stably expression of relevant plasmids and randomly divided into indicated groups (five mice per group). To assess the in vivo effects of cycloleucine, the xenografted tumors had reached approximately 5 mm in diameter from mice and then these xenografted mice were feed with Vehicle or cycloleucine (25 mg/kg twice weekly) and tumor volume were measured every 3 day. Tumor volume was estimated as 0.5 × a² × b (where a and b represent a tumors short and long diameter, respectively). Mice were euthanized after 7 weeks and the tumors were measured a final time.
Response Summary	m6A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated Transcriptional coactivator YAP1 (YAP1) expression and inhibiting miR-107/LATS2-mediated YAP activity in non-small cell lung cancer.

Acute myocardial infarction [ICD-11: BA41]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[50]
Responsed Disease	Acute myocardial infarction [ICD-11: BA41]
Target Regulation	Up regulation
In-vivo Model	Cas9 and sgRNA were microinjected into the fertilized eggs of C57BL/6J mice, which were then transplanted to obtain positive F0 mice. The statuses of F0 mice were confirmed by PCR and sequencing. Next, positive F0 mice were mated with C57BL/6J mice to yield stable F1 generation mice. F1 and F2 transgenic mice were used in this study.
Response Summary	ALKBH5-mediated m6A demethylation improved the mRNA stability of YTH N6-methyladenosine RNA-binding protein 1 (YTHDF1), thereby increasing its expression, which consequently promoted the translation of Transcriptional coactivator YAP1 (YAP1).This finding suggests a novel potential therapeutic strategy for myocardial infarction cardiac regeneration.

Transferrin receptor protein 1 (TFRC)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	Neutrophils	Mus musculus
Treatment: Alkbh5-/- neutrophils Control: Wild type neutrophils		GSE198316
Regulation		logFC: -1.41E+00 p-value: 1.41E-09
More Results	Click to View More RNA-seq Results

Acute myocardial infarction [ICD-11: BA41]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[38]
Responsed Disease	Acute myocardial infarction [ICD-11: BA41]
Cell Process	Lysosomal escape
In-vivo Model	Wild-type C57 (female, 12-16 weeks old), ALKBH5 /- mice (female and male, 12-16 weeks old), and SPF-grade SD rats (female, 180-230 g) were used to establish the AMI model.Sodium pentobarbital diluted to 10 mg/mL was used to anesthetize the mice or rat at the dose of 50 mg/kg through an intraperitoneal injection. By using a small animal ventilator with endotracheal intubation, thoracotomy was performed at the left fourth intercostal region. The heart was exposed, and the left anterior descending coronary artery (LCA) was occluded through a 6-0 silk suture that was placed 2-3 mm distal to the origin of the LCA with a slipknot. The apical region turned white, and ST segment elevation and T wave inversion of ECG showed that the AMI model was successfully established. Forty-five minutes after ischemia, the slipknot was released, and the ischemic region was reperfused. PBS (0.2 ml), HSSS (23.5 mg/kg, 0.2 ml), IOX1 (10 mg/kg, 0.2 ml), and HSSS-I (33.5 mg/kg, containing 10 mg/kg IOX1, 0.2 ml) were administered through caudal vein injection for 14 days at the frequency of one time per day.
Response Summary	IOX1, which is an inhibitor of ALKBH5, was loaded on HSSS to form HSSS-I, which could effectively ameliorate cardiac dysfunction in acute myocardial infarction. The surface-modified bioengineered ferritin nanocage targeted the dying cells in the infarct area under the guidance of Scarf1. These cells were then phagocytosed through recognition of their Transferrin receptor protein 1 (TFRC) receptor.

Transforming acidic coiled-coil-containing protein 3 (TACC3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	HaCAT cell line	Homo sapiens
Treatment: siALKBH5 HaCAT cells Control: siControl HaCAT cells		GSE211076
Regulation		logFC: 7.07E-01 p-value: 2.85E-14
More Results	Click to View More RNA-seq Results

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[51]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Up regulation
Pathway Response	Signaling pathways regulating pluripotency of stem cells			hsa04550
Cell Process	Self-renewal
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	MOLM-13	Adult acute myeloid leukemia	Homo sapiens	CVCL_2119
	Mono-Mac-6	Adult acute monocytic leukemia	Homo sapiens	CVCL_1426
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	NB4	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
	NOMO-1	Adult acute monocytic leukemia	Homo sapiens	CVCL_1609
	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	U-937	Adult acute monocytic leukemia	Homo sapiens	CVCL_0007
In-vivo Model	gRNA and Cas9 mRNA were mixed at concentration of 50 and 100 ng/ul, respectively, and injected to the cytoplasm of one-cell-stage embryos of C57BL/6 genetic background.
Response Summary	ALKBH5 exerts tumor-promoting effects in acute myeloid leukemia by post-transcriptional regulation of its critical targets such as Transforming acidic coiled-coil-containing protein 3 (TACC3), a prognosis-associated oncogene in various cancers.

Tyrosine-protein kinase JAK2 (JAK2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	NOMO-1 cell line	Homo sapiens
Treatment: shALKBH5 NOMO-1 cells Control: shNS NOMO-1 cells		GSE144968
Regulation		logFC: 1.17E+00 p-value: 2.74E-05
More Results	Click to View More RNA-seq Results

Malignant mixed epithelial mesenchymal tumour [ICD-11: 2B5D]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[52]
Responsed Disease	Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	JAK-STAT signaling pathway			hsa04630
In-vitro Model	HO8910-DDP (HO8910 underwent continuous stepwise exposure to increasing concentrations of cisplatin to create the cisplatin-resistant cell lines HO8910-DDP)
	HO-8910	Endocervical adenocarcinoma	Homo sapiens	CVCL_6868
	A2780-DDP (A2780 underwent continuous stepwise exposure to increasing concentrations of cisplatin to create the cisplatin-resistant cell line)
	A2780	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
In-vivo Model	About 5× 10⁶ cells were injected subcutaneously into the axilla of the female athymic BALB/C nude mice (4 week-old, 18-20?g). When the average tumor size reached approximately 100mm³ (after 1 week), mice were then randomized into two groups and treated with cisplatin (5 mg/kg) or normal saline (NS) weekly.
Response Summary	The ALKBH5-HOXA10 loop jointly activates the JAK2/STAT3 signaling pathway by mediating Tyrosine-protein kinase JAK2 (JAK2) m6A demethylation, promoting epithelial ovarian cancer resistance to cisplatin.

Tyrosine-protein kinase receptor UFO (AXL)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: 9.65E-01 p-value: 8.11E-04
More Results	Click to View More RNA-seq Results

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[53]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	mRNA stability
In-vitro Model	MOLM-13	Adult acute myeloid leukemia	Homo sapiens	CVCL_2119
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
In-vivo Model	Congenic recipient mice (CD45.2) at 8-10 weeks old were used for AML transplantation, and CD45.1 recipients at 8-10 weeks old were used for normal hematopoietic transplantation assays.
Response Summary	Expression of m6A demethylase ALKBH5 is regulated by chromatin state alteration during leukemogenesis of human acute myeloid leukemia (AML), and ALKBH5 is required for maintaining leukemia stem cell (LSC) function but is dispensable for normal hematopoiesis. ALKBH5 affects mRNA stability of receptor tyrosine kinase Tyrosine-protein kinase receptor UFO (AXL) in an m6A-dependent way.

Ubiquitin carboxyl-terminal hydrolase 1 (USP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: -6.03E-01 p-value: 1.12E-02
More Results	Click to View More RNA-seq Results

Mature T-cell lymphoma [ICD-11: 2A90]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[54]
Responsed Disease	Mature T-cell lymphoma [ICD-11: 2A90]
Responsed Drug	dexamethasone		Approved	Drug Info
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	CEM/C1	T acute lymphoblastic leukemia	Homo sapiens	CVCL_3496
	CCRF-CEM C7	T acute lymphoblastic leukemia	Homo sapiens	CVCL_6825
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Adult male C57BL/6J mice (weighting 18-25 g) were obtained from Laboratory Animal Center, Zhengzhou University. Mice were subcutaneously injected with 1 × 10⁷ CEM-C1 cells for tumorigenesis and randomly divided into four group: control group; control + Dex; sh-RNA + Dex; sh-USP1 + Dex. Mice treatment with Dex were intraperitoneally injected with 8 mg/kg Dex every day for 10 consecutive days after tumor growth and mice treatment with sh-RNA or sh-USP1 were injected intravenously with 2 mg/Kg sh-RNA or USP1 sh-RNA. The control group of mice were injected with the same volume of normal saline. After the treatment of each group, the mice were housed and fed in a room with an ambient temperature of 25℃, and the survival time, weight of the mice, and tumor weight were recorded. When rats were sacrificed, tissues were harvested for Western blot analysis.
Response Summary	ALKBH5 and Ubiquitin carboxyl-terminal hydrolase 1 (USP1) were upregulated in T-cell acute lymphoblastic leukemia, and ALKBH5-mediated m6A modification increased USP1 and Aurora B expression. Silencing USP1 increased CEM-C1 cell sensitivity to dexamethasone, reduced cell invasion, promoted cell apoptosis, and ameliorated glucocorticoid receptor (GR) expression.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[54]
Responsed Disease	Mature T-cell lymphoma [ICD-11: 2A90]
Responsed Drug	Glucocorticoid		Investigative	Drug Info
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	CEM/C1	T acute lymphoblastic leukemia	Homo sapiens	CVCL_3496
	CCRF-CEM C7	T acute lymphoblastic leukemia	Homo sapiens	CVCL_6825
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Adult male C57BL/6J mice (weighting 18-25 g) were obtained from Laboratory Animal Center, Zhengzhou University. Mice were subcutaneously injected with 1 × 10⁷ CEM-C1 cells for tumorigenesis and randomly divided into four group: control group; control + Dex; sh-RNA + Dex; sh-USP1 + Dex. Mice treatment with Dex were intraperitoneally injected with 8 mg/kg Dex every day for 10 consecutive days after tumor growth and mice treatment with sh-RNA or sh-USP1 were injected intravenously with 2 mg/Kg sh-RNA or USP1 sh-RNA. The control group of mice were injected with the same volume of normal saline. After the treatment of each group, the mice were housed and fed in a room with an ambient temperature of 25℃, and the survival time, weight of the mice, and tumor weight were recorded. When rats were sacrificed, tissues were harvested for Western blot analysis.
Response Summary	ALKBH5 and Ubiquitin carboxyl-terminal hydrolase 1 (USP1) were upregulated in T-cell acute lymphoblastic leukemia, and ALKBH5-mediated m6A modification increased USP1 and Aurora B expression. Silencing USP1 increased CEM-C1 cell sensitivity to dexamethasone, reduced cell invasion, promoted cell apoptosis, and ameliorated glucocorticoid receptor (GR) expression.

Ubiquitin carboxyl-terminal hydrolase 22 (USP22)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: -2.53E+00 p-value: 1.55E-42
More Results	Click to View More RNA-seq Results

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[11]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Up regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Proteasome pathway degradation
In-vitro Model	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	OS-17	Osteosarcoma	Homo sapiens	CVCL_9992
	IMR-90	Normal	Homo sapiens	CVCL_0347
	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
	143B	Osteosarcoma	Homo sapiens	CVCL_2270
In-vivo Model	For tumor xenograft studies, 143B cells stably expressing scrambled shRNA or ALKBH5 shRNA (1 × 10⁶) were injected subcutaneously into the flanks of 4-week-old athymic nude mice.
Response Summary	In osteosarcoma, ALKBH5 mediates its protumorigenic function by regulating m6A levels of histone deubiquitinase Ubiquitin carboxyl-terminal hydrolase 22 (USP22) and the ubiquitin ligase RNF40.

Ubiquitin-conjugating enzyme E2 C (UBE2C)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	HaCAT cell line	Homo sapiens
Treatment: siALKBH5 HaCAT cells Control: siControl HaCAT cells		GSE211076
Regulation		logFC: 9.83E-01 p-value: 3.48E-52
More Results	Click to View More RNA-seq Results

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[55]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Up regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Cell invasion
	Ubiquitination degradation
	Cell autophagy
In-vitro Model	PLA-801D	Lung giant cell carcinoma	Homo sapiens	CVCL_7110
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	HBEC (Human lung cancer cell)
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
Response Summary	Deregulated Ubiquitin-conjugating enzyme E2 C (UBE2C)-autophagy repression axis drives NSCLC progression which renders varieties of potential molecular targets in cancer therapy of NSCLC. UBE2C is repressed post-transcriptionally via tumor suppressor miR-381 and epitranscriptionally stabilized with maintenance of lower m6A level within its mature RNAs due to the upregulation of m6A demethylase ALKBH5 in NSCLC.

Zinc finger protein SNAI1 (SNAI1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	CAG cell line	Homo sapiens
Treatment: shALKBH5 CAG cells Control: shNC CAG cells		GSE180214
Regulation		logFC: 1.03E+00 p-value: 7.72E-05
More Results	Click to View More RNA-seq Results

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[13]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Target Regulation	Down regulation
Pathway Response	Adherens junction			hsa04520
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
Response Summary	ALKBH5 overexpression incurred a significant reduction in iron-regulatory protein IRP2 and the modulator of epithelial-mesenchymal transition (EMT) Zinc finger protein SNAI1 (SNAI1). Owing to FBXL5-mediated degradation, ALKBH5 overexpression incurred a significant reduction in iron-regulatory protein IRP2 and the modulator of epithelial-mesenchymal transition (EMT) SNAI1. ALKBH5 in protecting against PDAC through modulating regulators of iron metabolism and underscore the multifaceted role of m6A in pancreatic cancer.

KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	NOMO-1 cell line	Homo sapiens
Treatment: shALKBH5 NOMO-1 cells Control: shNS NOMO-1 cells		GSE144968
Regulation		logFC: 1.52E+00 p-value: 9.12E-06
More Results	Click to View More RNA-seq Results

Laryngeal cancer [ICD-11: 2C23]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[56]
Responsed Disease	Laryngeal cancer [ICD-11: 2C23]
Target Regulation	Up regulation
Cell Process	Cell proliferation and metastasis
In-vitro Model	AMC-HN-8	Laryngeal squamous cell carcinoma	Homo sapiens	CVCL_5966
	HOK	Normal	Hexagrammos otakii	CVCL_YE19
	Tu 212	Head and neck squamous cell carcinoma	Homo sapiens	CVCL_4915
In-vivo Model	1 × 10⁶ (100 ul) cells of infected and uninfected by lentiviral were, respectively, injected subcutaneously into nude mice which divided randomly into scramble group and shKCNQ1OT1-1 group.
Response Summary	ALKBH5 mediates KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) expression via an m6A-YTHDF2-dependent manner and KCNQ1OT1 could directly bind to HOXA9 to further regulate the proliferation, invasion and metastasis of laryngeal squamous cell carcinoma cells.

Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	NOMO-1 cell line	Homo sapiens
Treatment: shALKBH5 NOMO-1 cells Control: shNS NOMO-1 cells		GSE144968
Regulation		logFC: 1.03E+00 p-value: 3.88E-04
More Results	Click to View More RNA-seq Results

Urinary/pelvic organs injury [ICD-11: NB92]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[57]
Responsed Disease	Injury of kidney [ICD-11: NB92.0Z]
Target Regulation	Up regulation
Cell Process	Cell cycle
	Cell proliferation
	Cell apoptosis
In-vitro Model	HK2	Normal	Acipenser baerii	CVCL_YE28
Response Summary	ALKBH5 could up-regulate Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) expression by demethylation. Furthermore, dexmedetomidine inhibited the expression of ALKBH5 in LPS-treated HK-2 cells. Dexmedetomidine suppressed the biological behavior of HK-2 cells treated with LPS by inhibiting the expression of ALKBH5 in vitro, which provides potential targets for the prevention and treatment of sepsis-induced kidney injury. Dexmedetomidine suppressed the biological behavior of HK-2 cells treated with LPS by inhibiting the expression of ALKBH5 in vitro, which provides potential targets for the prevention and treatment of sepsis-induced kidney injury.

Nuclear paraspeckle assembly transcript 1 (NEAT1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	HaCAT cell line	Homo sapiens
Treatment: siALKBH5 HaCAT cells Control: siControl HaCAT cells		GSE211076
Regulation		logFC: -6.88E-01 p-value: 8.40E-87
More Results	Click to View More RNA-seq Results

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[58]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Target Regulation	Down regulation
Pathway Response	Transcriptional misregulation in cancer			hsa05202
Cell Process	Immune
In-vitro Model	GL261	Mouse glioblastoma	Mus musculus	CVCL_Y003
	U87 (A primary glioblastoma cell line)
In-vivo Model	Male C57BL/6 mice (4-6 weeks old) were used in all tumor allografting experiments and transplanted with GL261-luc cells (1×10⁵) into the frontal lobes of brains.
Response Summary	Hypoxia-induced ALKBH5 erased m6A deposition from the lncRNA NEAT1, stabilizing the transcript and facilitating Nuclear paraspeckle assembly transcript 1 (NEAT1)-mediated paraspeckle assembly. Ectopic expression of CXCL8 in ALKBH5-deficient glioblastoma multiforme cells partially restored TAM recruitment and tumor progression.

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[59]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Cell Process	Cell proliferation and metastasis
In-vitro Model	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	GES-1	Normal	Homo sapiens	CVCL_EQ22
	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
Response Summary	ALKBH5 promotes Gastric cancer invasion and metastasis by demethylating the lncRNA Nuclear paraspeckle assembly transcript 1 (NEAT1).

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[60]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Cell Process	Cell proliferation and migration
Cell Process	Cell apoptosis
In-vitro Model	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	HIEC (Normal intestinal epithelial cells)
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	To establish xenograft model, RKO cells (1 × 10⁷) tansduced with si-control (si-NC) or si-ALKBH5 or si-ALKBH5+NEAT1 were injected subcutaneously into the right flank of the nude mice (n = 6 each group) every 5 days for 4 times.
Response Summary	ALKBH5 knockdown suppressed malignant behavior of colon cancer partially through Nuclear paraspeckle assembly transcript 1 (NEAT1) by demethylation in vitro and vivo, suggesting that ALKBH5-NEAT1 axis is a potential therapeutic target for colon cancer treatment.

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[61]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Cell Process	Cell proliferation and migration
Cell Process	Cell apoptosis
In-vitro Model	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
Response Summary	ALKBH5 could up-regulate Nuclear paraspeckle assembly transcript 1 (NEAT1) expression by inhibiting m6A enrichment. ALKBH5-induced NEAT1 promoted cell proliferation and migration of HCC by sponging miR-214 in vitro, which provided a potential therapeutic target for HCC.

Infantile hemangioma [ICD-11: 2E81]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[62]
Responsed Disease	Infantile hemangioma [ICD-11: 2E+81]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	XPTS-1	Infantile hemangioma	Homo sapiens	CVCL_9U60
	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	ALKBH5 knockdown suppressed cell proliferation, migration and invasion of infantile hemangioma cells, while promoting cell apoptosis. ALKBH5 promoted lncRNA Nuclear paraspeckle assembly transcript 1 (NEAT1) expression by reducing the m6A modification of lncRNA NEAT1.

Pvt1 oncogene (PVT1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	NOMO-1 cell line	Homo sapiens
Treatment: shALKBH5 NOMO-1 cells Control: shNS NOMO-1 cells		GSE144968
Regulation		logFC: -1.38E+00 p-value: 6.15E-03
More Results	Click to View More RNA-seq Results

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[63]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	143B	Osteosarcoma	Homo sapiens	CVCL_2270
	HOS	Osteosarcoma	Homo sapiens	CVCL_0312
	SaOS-LM7	Osteosarcoma	Homo sapiens	CVCL_0515
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	NHOst (Normal human osteoblast cells)
	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
In-vivo Model	Indicated stable 143B cells were subcutaneously injected into nude mice.
Response Summary	ALKBH5 decreased the m6A modification of Pvt1 oncogene (PVT1), thus inhibiting the binding of reader protein YTHDF2 in PVT1. ALKBH5-mediated PVT1 upregulation promoted the osteosarcoma cell proliferation in vitro and tumor growth in vivo.

RMRP

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: -1.09E+00 p-value: 4.52E-03
More Results	Click to View More RNA-seq Results

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[64]
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	XWLC-05	Lung adenocarcinoma	Homo sapiens	CVCL_IQ71
In-vivo Model	The mice were maintained in cages under standard environmental conditions (temperature 25 ± 2 ℃, humidity 55 ± 5% and 12-h light/12-h dark cycle) and given free access to food and tap water. All mice were randomly divided into three groups with 6 in each group. To establish xenograft model, A549 cells (1 × 10⁷) transfected with si-control (si-NC), si-ALKBH5 or si-ALKBH5 + RMRP were injected subcutaneously into a single side of the armpit of each mouse.
Response Summary	ALKBH5 knockdown, was able to inhibit malignant behavior of lung adenocarcinoma by regulating RMRP expression via demethylation. RMRP and ALKBH5 therefore represent promising therapeutic targets for lung adenocarcinoma.

Casein kinase II subunit alpha' (CSNK2A2)

Target Gene

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[65]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Metabolic pathways			hsa01100
Pathway Response	Glycolysis / Gluconeogenesis			hsa00010)
Cell Process	Glycolysis
In-vitro Model	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	J82	Bladder carcinoma	Homo sapiens	CVCL_0359
	253J	Bladder carcinoma	Homo sapiens	CVCL_7935
	5637	Bladder carcinoma	Homo sapiens	CVCL_0126
Response Summary	knockdown of ALKBH5 promoted bladder cancer cell proliferation, migration, invasion, and decreased cisplatin chemosensitivity, ALKBH5 inhibited the progression and sensitized bladder cancer cells to cisplatin through a Casein kinase II subunit alpha' (CSNK2A2)-mediated glycolysis pathway in an m6A-dependent manner.

Cellular tumor antigen p53 (TP53/p53)

Target Gene

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[66]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Response Summary	Deletion of METTL16 or ALKBH5 predicted poor OS and DFS of hepatocellular carcinoma (HCC) patients. And this study found significant associations between the genetic alterations and clinicopathological features as well as Cellular tumor antigen p53 (TP53/p53) alteration.

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[29]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Up regulation
Pathway Response	p53 signaling pathway			hsa04115
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	Cells at 1 × 10⁶ were subcutaneously injected into the mice similarly to nude mice. Twenty-eight days later, grafted tumors were collected and morphologically analyzed.
Response Summary	Knockdown of Cellular tumor antigen p53 (TP53/p53) or inhibition of p53's transcriptional activity by addition of its specific inhibitor PFT-Alpha decreased expression of ALKBH5 and Cancer stem cells' malignancies, the pivotal role of ALKBH5 in Cancer stem cells derived from nonsmall-cell lung cancer and highlight the regulatory function of the p53/ALKBH5 axis in modulating CSC progression. p53 transcriptionally regulates PRRX1, which is consistent with our previous report.

Female reproductive system disorders [ICD-11: SC4Y]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[67]
Responsed Disease	Female reproductive system disorders [ICD-11: SC4Y]
Pathway Response	p53 signaling pathway			hsa04115
In-vitro Model	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
In-vivo Model	Neo-resistant recombinant ESCs were analyzed for correct 3' and 5' targeting through hybridization by standard protocols, and we identified seven correctly targeted clones. Following ESC cell injection, several high-percentage chimera males were born. These were bred with Cre-expressing mice, and Cre-mediated excision of Alkbh5 exon 1 was tested in 26 agouti F1 pups. Two animals tested positive for the excised allele. These two mice, heterozygous for the constitutive allele (Alkbh5^+/-), were analyzed by Southern blot analysis and used for further breeding to generate Alkbh5^-/- mice.
Response Summary	ALKBH5 as another mammalian demethylase that oxidatively reverses m(6)A in mRNA in vitro and in vivo. Alkbh5-deficient male mice have increased m(6)A in mRNA and are characterized by impaired fertility resulting from apoptosis that affects meiotic metaphase-stage spermatocytes. Identified in mouse testes 1,551 differentially expressed genes that cover broad functional categories and include spermatogenesis-related mRNAs involved in the Cellular tumor antigen p53 (TP53/p53) functional interaction network.

ELAV-like protein 1 (HuR/ELAVL1)

Target Gene

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[68]
Responsed Disease	Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Target Regulation	Up regulation
Cell Process	RNA stability
Cell Process	Cell apoptosis
In-vitro Model	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
In-vivo Model	For tumor xenograft studies, MDA-MB-231 cells transfected with scrambled-siRNA or METTL14-siRNA or ALKBH5-siRNA (2 × 10⁶) were mixed with Matrigel and injected subcutaneously in the flank of 6-week-old female athymic nude mice.
Response Summary	METTL14 and ALKBH5 determine the m6A status of target genes by controlling each other's expression and by inhibiting m6A reader YTHDF3 (YTH N 6-methyladenosine RNA binding protein 3), which blocks RNA demethylase activity. ALKBH5/METTL14 constitute a positive feedback loop with RNA stability factor ELAV-like protein 1 (HuR/ELAVL1) to regulate the stability of target transcripts. This study unveils a previously undefined role for m6A in cancer and shows that the collaboration among writers-erasers-readers sets up the m6A threshold to ensure the stability of progrowth/proliferation-specific genes, and protumorigenic stimulus.

Frizzled-10 (FZD10)

Target Gene

Malignant mixed epithelial mesenchymal tumour [ICD-11: 2B5D]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[69]
Responsed Disease	Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Responsed Drug	PARPi		Investigative	Drug Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
In-vitro Model	UWB1.289	Ovarian carcinoma	Homo sapiens	CVCL_B079
In-vitro Model	PEO1	Ovarian cystadenocarcinoma	Homo sapiens	CVCL_2686
In-vivo Model	2 × 10⁷ PARP inhibitor resistant PEO1 cells were suspended in 200 uL PBS : Matrigel (1:1) unilaterally injected subcutaneously into the right dorsal flank of 6-8 week-old female immunocompromised non-obese diabetic/severe combined immunodeficiency (NOD/SCID) gamma (NSG) mice. When the average tumor size reached ~100 mm3, the mice were then randomized into four groups and treated with vehicle control, Olaparib (50 mg/kg), XAV939 (5 mg/kg) or a combination daily for 18 days.
Response Summary	Downregulation of m6A demethylases FTO and ALKBH5 was sufficient to increase Frizzled-10 (FZD10) mRNA m6A modification and reduce PARPi sensitivity, the finding elucidates a novel regulatory mechanism of PARPi resistance in EOC by showing that m6A modification of FZD10 mRNA contributes to PARPi resistance in BRCA-deficient EOC cells via upregulation of Wnt/Bete-catenin pathway.

Histone deacetylase 4 (HDAC4)

Target Gene

Motor neuron disease [ICD-11: 8B60]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[70]
Responsed Disease	Progressive muscular atrophy [ICD-11: 8B60.3]
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway	hsa04068
In-vivo Model	Mice bearing the Alkbh5-floxed allele (Alkbh5 ^fl/fl, Cyagen) were crossed with transgenic mice expressing Cre recombinase under the control of the Myl1 promoter (Myl1-Cre; Stock No: 024713, The Jackson Laboratory) to generate muscle-specific Alkbh5 knockout mice (Myl1-Cre;Alkbh5 ^fl/fl ). Littermate Alkbh5^fl/fl mice were used as controls. Genotyping by tail DNA and PCR were performed at 4 weeks of age.
Response Summary	ALKBH5 demethylates and stabilizes Hdac4 mRNA. Histone deacetylase 4 (HDAC4) interacts with and deacetylates FoxO3, resulting in a significant increase in FoxO3 expression. These results suggest that ALKBH5 is a potential therapeutic target for neurogenic muscle atrophy.

Homeobox protein NANOG (NANOG)

Target Gene

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[71]
Responsed Disease	Glioma [ICD-11: 2A00.0]
Responsed Drug	Temozolomide		Approved	Drug Info
Target Regulation	Up regulation
Cell Process	Cellular Processes
	Cell growth and death
	Cell apoptosis
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	U251 (Fibroblasts or fibroblast like cells)
	U87 (A primary glioblastoma cell line)
In-vivo Model	U251/TR cells (2 × 10⁶ per mouse) with stable transfection of sh-circ_0072083 or sh-NC were subcutaneously injected into mice.
Response Summary	In glioma, hsa_circ_0072083 could regulate Homeobox protein NANOG (NANOG) and ALKBH5 via targeting miR-1252-5p to control temozolomide resistance. circ_0072083 silence reduced NANOG expression via blocking ALKBH5-mediated demethylation.

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[72]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Up regulation
Pathway Response	HIF-1 signaling pathway			hsa04066
Cell Process	Signaling pathways regulating pluripotency of stem cells (hsa04550)
In-vitro Model	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	HCC1954	Breast ductal carcinoma	Homo sapiens	CVCL_1259
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MDA-MB-435	Amelanotic melanoma	Homo sapiens	CVCL_0417
	SUM-149 (Human breast cancer cell SUM149)
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	ZR75.1 A3	Invasive breast carcinoma	Homo sapiens	CVCL_YX82
In-vivo Model	A total of 1,000 breast cancer cells were injected into the mammary fat pad of 6-8-wk-old female NSG mice in a 1:1 suspension of Matrigel (BD Biosciences) in PBS solution. At 10 wk after injection, mice were examined for the presence of tumors, which were harvested for analysis.
Response Summary	Homeobox protein NANOG (NANOG) activity does not merely compensate for reduced O2 levels but significantly increases ALKBH5, JMJD2C, and TET1 activity in hypoxic breast cancer cells, leading to transcriptional and posttranscriptional changes in gene expression that promote the specification and/or maintenance of BCSCs. ALKBH5 overexpression decreased Homeobox protein NANOG (NANOG) mRNA methylation, increased NANOG levels, and increased the percentage of BCSCs,

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[74]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]
Target Regulation	Up regulation
Cell Process	Cell invasion
In-vitro Model	HEY	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0297
	HO-8910	Endocervical adenocarcinoma	Homo sapiens	CVCL_6868
	OVCAR-3	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0465
	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In-vivo Model	Female athymic BALB/c nude mice (4-week-old) were provided (SLAC Laboratory Animal Co. Ltd.). The animals were raised in a pathogen-free animal laboratory and randomly divided into the control or experimental group (six mice in each group).
Response Summary	Homeobox protein NANOG (NANOG) served as a target in ALKBH5-mediated m6A modification in ovarian cancer.

Integrin alpha-6 (ITGA6)

Target Gene

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[75]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Pathway Response	Cell adhesion molecules			hsa04514
Cell Process	Cell adhesion
	Cell migration
	Cell invasion
In-vitro Model	5637	Bladder carcinoma	Homo sapiens	CVCL_0126
	HEK293T	Normal	Homo sapiens	CVCL_0063
	J82	Bladder carcinoma	Homo sapiens	CVCL_0359
	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
In-vivo Model	For the subcutaneous implantation model, 1 × 10⁷ cells were subcutaneously implanted into 5-week-old BALB/cJNju-Foxn1nu/Nju nude mice.
Response Summary	m6A writer METTL3 and eraser ALKBH5 altered cell adhesion by regulating Integrin alpha-6 (ITGA6) expression in bladder cancer cells. m6A is highly enriched within the ITGA6 transcripts, and increased m6A methylations of the ITGA6 mRNA 3'UTR promotes the translation of ITGA6 mRNA via binding of the m6A readers YTHDF1 and YTHDF3. Inhibition of ITGA6 results in decreased growth and progression of bladder cancer cells in vitro and in vivo.

Iron-responsive element-binding protein 2 (IRP2)

Target Gene

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[13]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Target Regulation	Down regulation
Pathway Response	Adherens junction			hsa04520
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
Response Summary	ALKBH5 overexpression incurred a significant reduction in iron-regulatory protein Iron-responsive element-binding protein 2 (IRP2) and the modulator of epithelial-mesenchymal transition (EMT) SNAI1. Owing to FBXL5-mediated degradation, ALKBH5 overexpression incurred a significant reduction in iron-regulatory protein IRP2 and the modulator of epithelial-mesenchymal transition (EMT) SNAI1. ALKBH5 in protecting against PDAC through modulating regulators of iron metabolism and underscore the multifaceted role of m6A in pancreatic cancer.

Mammalian target of rapamycin complex 2 (mTORC2)

Target Gene

Oral cavity/oesophagus/stomach in situ carcinoma [ICD-11: 2E60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[76]
Responsed Disease	Esophageal squamous cell carcinoma [ICD-11: 2B70.1]
Cell Process	Cell proliferation and invasion
In-vitro Model	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
In-vitro Model	Eca-109	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898
Response Summary	ALKBH5 as a demethylase was lowly expressed in cancer progression of esophageal squamous cell carcinoma (ESCC) and acts as a crucial component in ESCC progression.

Lupus erythematosus [ICD-11: 4A40]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[77]
Responsed Disease	Lupus erythematosus [ICD-11: 4A40]
In-vitro Model	PBMCs (Human peripheral blood mononuclear cells (PBMCs) are isolated from peripheral blood and identified as any blood cell with a round nucleus)
Response Summary	Functionally, the overexpression of ALKBH5 promoted apoptosis and inhibited the proliferation of T cells. ALKBH5 expression is downregulated in systemic lupus erythematosus (SLE) patients and could affect the apoptosis and proliferation of T cells.

Retinoic acid-induced protein 1 (RAI1)

Target Gene

Esophageal cancer [ICD-11: 2B70]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[78]
Responsed Disease	Esophageal cancer [ICD-11: 2B70]
Target Regulation	Down regulation
Response Summary	ALKBH5 demethylated pri-miR-194-2 and inhibited miR-194-2 biogenesis through an m6A/DGCR8-dependent manner. ALKBH5/miR-194-2/Retinoic acid-induced protein 1 (RAI1) axis was also validated in clinical samples. This study revealed ALKBH5 in miRNAs biogenesis and provide novel insight for developing treatment strategies in esophageal cancer.

Ubiquitin conjugating enzyme E2 I (UBE2I/UBC9)

Target Gene

Diseases of the circulatory system [ICD-11: BE2Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[43]
Responsed Disease	Diseases of the circulatory system [ICD-11: BE2Z]
Target Regulation	Up regulation
Pathway Response	Apoptosis			hsa04210
	Chemical carcinogenesis - reactive oxygen species			hsa05208
Cell Process	Oxygen species(ROS)-induced stress
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	For the ROS-induced DNA damage analysis, the indicated cell lines were treated with or without 100 uM hydrogen peroxide (H₂O₂), or 80 uM Carbonyl cyanide m-chlorophenylhydrazone (CCCP) for 6 hours. For the in vivo ROS study, DMSO and 5 mg/kg CCCP was intraperitoneally injected in to three pairs of mice.
Response Summary	ROS promotes ALKBH5 SUMOylation through activating ERK/EPHB2/JNK signaling, leading to inhibition of ALKBH5 m6A demethylase activity by blocking substrate accessibility. Post-translational modification of ALKBH5 regulates ROS-induced DNA damage response. ROS specifically promotes ALKBH5 but not FTO, METTL3 and METTL14 SUMOylation by enhancing the interaction of ALKBH5 and Ubiquitin conjugating enzyme E2 I (UBE2I/UBC9) and inhibiting the association between ALKBH5 and SENP1.

Wnt inhibitory factor 1 (WIF1)

Target Gene

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[79]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Responsed Drug	Gemcitabine		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
In-vitro Model	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	Capan-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0237
	Capan-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0026
	CFPAC-1	Cystic fibrosis	Homo sapiens	CVCL_1119
	HPDE6c7	Normal	Homo sapiens	CVCL_0P38
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
Response Summary	ALKBH5 overexpression sensitizes Pancreatic cancer cells to gemcitabine treatment, and it represses PDAC tumorigenesis by reducing m6A levels of Wnt inhibitory factor 1 (WIF1) and hindering activation of Wnt signaling.

Growth arrest specific 5 (GAS5)

Target Gene

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[80]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulation	Up regulation
Cell Process	Cell proliferation and metastasis
In-vitro Model	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
	Ca Ski	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	Normal cervical epithelium cell line (HCvEpC) (Isolated from cervical tissue)
In-vivo Model	200 uL PBS containing 1×10⁷ cells of stable cells were subcutaneously injected into male BALB/c athymic nude mice (6-week old, 18-20 g).
Response Summary	The GAS5-AS1 expression in cervical cancer tissues was markedly decreased when compared with that in the adjacent normal tissues. GAS5-AS1 interacted with the tumor suppressor Growth arrest specific 5 (GAS5), and increased its stability by interacting with RNA demethylase ALKBH5 and decreasing GAS5 N6-methyladenosine (m6A) modification. m6A-mediated GAS5 RNA degradation relied on the m6A reader protein YTHDF2-dependent pathway.

KCNK15 and WISP2 antisense RNA 1 (KCNK15-AS1)

Target Gene

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[81]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Target Regulation	Up regulation
Cell Process	Epithelial-mesenchymal transition
Cell Process	Cell migration and invasion
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	HPDE6c7	Normal	Homo sapiens	CVCL_0P38
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
Response Summary	ALKBH5 inhibits pancreatic cancer motility by demethylating lncRNA KCNK15 and WISP2 antisense RNA 1 (KCNK15-AS1).

Long intergenic non-protein coding RNA 2598 (LINC02598/RP11)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[82]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Response Summary	Overexpression of METTL3 upregulates Long intergenic non-protein coding RNA 2598 (LINC02598/RP11) expression in colorectal cancer cells. Overexpression of ALKBH5 downregulates RP11 expression.

microRNA 107 (MIR107)

Target Gene

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[39]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Cell Process	Cell proliferation
	Cell invasion
	Cell migration
	Cell EMT
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	For the experiments, mice were injected with 5 × 10⁶ lung cancer cells with stably expression of relevant plasmids and randomly divided into indicated groups (five mice per group). To assess the in vivo effects of cycloleucine, the xenografted tumors had reached approximately 5 mm in diameter from mice and then these xenografted mice were feed with Vehicle or cycloleucine (25 mg/kg twice weekly) and tumor volume were measured every 3 day. Tumor volume was estimated as 0.5 × a² × b (where a and b represent a tumors short and long diameter, respectively). Mice were euthanized after 7 weeks and the tumors were measured a final time.
Response Summary	m6A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting microRNA 107 (MIR107)/LATS2-mediated YAP activity in non-small cell lung cancer.

microRNA 21 (MIR21)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[18]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Pathway Response	FoxO signaling pathway			hsa04068
In-vitro Model	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	FHC	Normal	Homo sapiens	CVCL_3688
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
Response Summary	ALKBH5 plays an antitumor role in colorectal cancer by modulating the FOXO3/microRNA 21 (MIR21)/SPRY2 axis, which not only suggests a regulatory effect between ALKBH5 and FOXO3, but also provides a new therapeutic direction for colorectal cancer.

microRNA 7-1 (MIR7-1)

Target Gene

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[2]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Pathway Response	mTOR signaling pathway			hsa04150
In-vitro Model	A2780	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	CoC1	Ovarian adenocarcinoma	Homo sapiens	CVCL_6891
	OVCAR-3	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0465
	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In-vivo Model	SKOV3 or A2780 cells were infected with the indicated lentiviral vectors and injected (5 × 10⁶ cells/mouse in 200 uL volume) subcutaneously into the left armpit of 6-week-old BALB/c nude mice. After 21 days, the animals were sacrificed to confirm the presence of tumors and weigh the established tumors
Response Summary	ALKBH5 is a tumor-promoting gene in epithelial ovarian cancer, which is involved in the mTOR pathway and microRNA 7-1 (MIR7-1)-Beclin1 complex. ALKBH5 activated EGFR-PIK3CA-AKT-mTOR signaling pathway. ALKBH5 inhibited autophagy of epithelial ovarian cancer through microRNA 7-1 (MIR7-1) and BCL-2.

miR-194-2

Target Gene

Esophageal cancer [ICD-11: 2B70]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[78]
Responsed Disease	Esophageal cancer [ICD-11: 2B70]
Target Regulation	Down regulation
Response Summary	ALKBH5 demethylated pri-miR-194-2 and inhibited miR-194-2 biogenesis through an m6A/DGCR8-dependent manner. ALKBH5/miR-194-2/RAI1 axis was also validated in clinical samples. This study revealed ALKBH5 in miRNAs biogenesis and provide novel insight for developing treatment strategies in esophageal cancer.

hsa-miR-143-3p

Target Gene

Aortic aneurysm or dissection [ICD-11: BD50]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[83]
Responsed Disease	Aortic aneurysm or dissection [ICD-11: BD50]
Target Regulation	Down regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	Cell apoptosis
In-vitro Model	IM-HAEC	Normal	Homo sapiens	CVCL_B5WL
In-vivo Model	Osmotic mini-pumps containing AngII (1 ug/kg/min, Enzo Bioche) were implanted in 7-week-old male mice. To interfere with the expression of KIAA1429, ALKBH5, or DDX6 in vivo, adeno-associated virus 9 (AAV9) vectors carrying a variety of overexpression plasmids or interfering RNA were randomly injected through the tail vein to C57BL/6N mice.
Response Summary	KIAA1429 is downregulated while ALKBH5 is upregulated in aortic tissues from aortic dissection patients. KIAA1429/ALKBH5-mediated m6A modifications can regulate the processing of hsa-miR-143-3p through interacting with the microprocessor protein DGCR8. KIAA1429 and ALKBH5 can oppositely regulate HASMC proliferation, HAEC apoptosis, and AD progression in AngII-infused mice via the miR-143-3p/DDX6 pathway.

hsa-mir-181b-1

Target Gene

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[49]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Down regulation
Cell Process	Cell growth
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
In-vivo Model	Three-week-old BABL/c female nude mice were randomized into three groups. 5 × 10⁶ 143B cells were subcutaneously injected in mice, and the tumor volume was assessed every 2 weeks. Eight weeks after injection, the animals were killed. The xenograft tumors were harvested and the tumor volumes were calculated by the standard formula: length × width²/2.
Response Summary	ALKBH5 is an anti-tumor factor or a pro-apoptotic factor, acting at least partially by suppressing YAP expression through dual mechanisms with direct m6A methylation of YAP and indirect downregulation of YAP level due to methylation of hsa-mir-181b-1. Further results revealed that m6A methylated pre-miR-181b-1 was subsequently recognized by m6A-binding protein YTHDF2 to mediate RNA degradation. However, methylated YAP transcripts were recognized by YTHDF1 to promote its translation. ALKBH5 overexpression was considered a new approach of replacement therapy for osteosarcoma treatment.

hsa-miR-21-5p

Target Gene

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[84]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	HEK293-A	Normal	Homo sapiens	CVCL_6910
Response Summary	In non-small cell lung cancer, m6A marks in mature hsa-miR-21-5p could directly affect its silencing potency towards target genes, which finally impaired its promotion to proliferation and motility. Depletion of the demethylase ALKBH5 altered the m6A abundance of miR-21-5p, thereby changing the expression levels of its target gene.

hsa-miR-320a-3p

Target Gene

Idiopathic interstitial pneumonitis [ICD-11: CB03]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[17]
Responsed Disease	Pulmonary Fibrosis [ICD-11: CB03.4]
Target Regulation	Down regulation
In-vitro Model	NIH 3T3	Normal	Mus musculus	CVCL_0594
In-vitro Model	MRC-5	Normal	Homo sapiens	CVCL_0440
In-vivo Model	For the mouse model of miR-320a-3p overexpression, a total of 24 male C57BL/6 mice were divided randomly into four groups (n = 6 in each group): saline, silica, silica plus AAV9-miR-NC, and silica plus AAV9-miR-320a-3p. The mice in the silica plus AAV9-miR-NC/AAV9-miR-320a-3p groups were anesthetized using the same method, then administered intratracheally 50 uL AAV9-miR-NC/AAV9-miR-320a-3p per mouse at a titer of 8 × 10¹² v. g./ml. Three weeks later, these mice were treated in the same way using anesthesia, saline, and silica as mentioned above. Subsequently, after 4 weeks, the mice were sacrificed, and the lungs were isolated and frozen at -80 ℃ for further study.
Response Summary	ALKBH5 promotes silica-induced lung fibrosis via the hsa-miR-320a-3p/FOXM1 axis or targeting FOXM1 directly.

hsa_circ_0008542

Target Gene

Diseases of the musculoskeletal system [ICD-11: FC0Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[85]
Responsed Disease	Diseases of the musculoskeletal system [ICD-11: FC0Z]
Target Regulation	Down regulation
Cell Process	RNA stability
In-vitro Model	RAW 264.7	Mouse leukemia	Mus musculus	CVCL_0493
In-vitro Model	MC3T3-E1	Normal	Mus musculus	CVCL_0409
In-vivo Model	circ_0008542, where rats were injected with exosomes containing circ_0008542 into the tail vein for 8 weeks.
Response Summary	METTL3 acts on the m6A functional site of 1956 bp in hsa_circ_0008542. RNA demethylase ALKBH5 inhibits the binding of circ_0008542 with miRNA-185-5p to correct the bone resorption process.

hsa_circ_0000417 (circCPSF6)

Target Gene

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[86]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Cell Process	Cell proliferation
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	B76.1/Huh7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_U443
	SNU-449	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0454
	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
In-vivo Model	HCC cells stably transfected with empty vector or circCPSF6 were subject to construct animal models, followed by the regular treatment of verteporfin, an inhibitor of YAP signaling.
Response Summary	circCPSF6 was dominated by ALKBH5-mediated demethylation, followed by the recognization and destabilization by YTHDF2. Meanwhile, circCPSF6 was upregulated in HCC specimens, and elevated hsa_circ_0000417 (circCPSF6) expression served as an independent prognostic factor for worse survival of patients with HCC.

Protein E6 (E6)

Target Gene

Malignant neoplasms of tonsil [ICD-11: 2B69]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[87]
Responsed Disease	Malignant neoplasms of tonsil [ICD-11: 2B69]
Target Regulation	Up regulation
In-vitro Model	WSU-HN26	Squamous cell carcinoma of the oral cavity	Homo sapiens	CVCL_5523
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	C33A2 (The C33A2 cell line originates from C33A and has the subgenomic HPV16 plasmid pBELsLuc stably integrated into the genome)
Response Summary	Overexpression of the ALKBH5 promoted production of intron retention on the human papillomavirus type 16 (HPV16) Protein E6 (E6) mRNAs thereby promoting E6 mRNA production. METLL3 induced production of intron-containing HPV16 E1 mRNAs over spliced E2 mRNAs and altered HPV16 L1 mRNA splicing in a manner opposite to ALKBH5. Overexpression of YTHDC1, enhanced retention of the E6-encoding intron and promoted E6 mRNA production. HPV16 mRNAs are m6A-methylated in tonsillar cancer cells.

Unspecific Target Gene

Viral infections [ICD-11: 1D9Y]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[88]
Responsed Disease	Viral infections [ICD-11: 1D9Y]
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	m6A is the most abundant internal modification described in eukaryotic mRNA and several viral RNA including human respiratory syncytial virus (HRSV) infection. METTL3/METTL14 m6A writer complex plays a negative role in HRSV infections protein synthesis and viral titers, while m6A erasers FTO and ALKBH5 had the opposite effect.

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[89]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Pathway Response	DNA replication	hsa03030
Cell Process	Homologous recombination
In-vitro Model	GBMSCs (Glioblastoma stem cells)
Response Summary	ALKBH5 contributes to the aggressiveness of GBM by favoring the invasion of GBMSCs.

Head and neck squamous carcinoma [ICD-11: 2B6E]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[91]
Responsed Disease	Head and neck squamous carcinoma [ICD-11: 2B6E]
Pathway Response	Ubiquitin mediated proteolysis	hsa04120
Cell Process	Ubiquitin-mediated proteolysis
	Cell apoptosis
Response Summary	In head and neck squamous cell carcinoma patients, a majority of highly expressed m6A regulatory genes is associated with poor OS, in particular ALKBH5, whereas YTHDC2 was associated with better prognosis.

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[92]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Pathway Response	Proteoglycans in cancer			hsa05205
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	GES-1	Normal	Homo sapiens	CVCL_EQ22
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
In-vivo Model	A total of 2×10⁶ tumor cells were suspended in 200 uL of PBS and injected the right flank of nude mice. The tumor sizes were measured weekly as soon as the tumors were measurable, and the tumor volumes were calculated using the following formula: volume (mm³) = width2 (mm²) × length (mm)/2. After 4 weeks, the mice were sacrificed, and the tumors were harvested.
Response Summary	ncRNA, lncNRON, exhibits oncogenic roles in the progression of gastric cancer. NRON, as a possible additional regulatory subunit of the m6A eraser, strengthens the m6A recognition of RNAs by m6A eraser ALKBH5 to enhance Nanog mRNA stability and expression.

Colon cancer [ICD-11: 2B90]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[93]
Responsed Disease	Colon cancer [ICD-11: 2B90]
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	For the animal studies, 6-week-old male athymic BALB/c nude mice were implanted with modified ALKBH5 expressing Hct116 or RKO cells (10⁵/ml, 200 ml) via lateral tail vein injection. All the mice were killed after 6 weeks, and the lungs were subjected to H&E staining.
Response Summary	the tumor repressive role of ALKBH5 in colon cancer. ALKBH5 was downregulated in human colon cancer tissues, where its decreased expression significantly correlated with distant metastasis and American Joint Committee on Cancer (AJCC) stage.

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[94]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Ubiquitination degradation
In-vitro Model	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
	THLE-2	Normal	Homo sapiens	CVCL_3803
In-vivo Model	For the subcutaneous implantation model, 5×10⁶ control and CASC11 overexpressing Huh7 cells were suspended in the 100 uL serum-free DMEM medium and then injected subcutaneously. For the metastatic model, 1×10⁵ control and CASC11 overexpressing Huh7 cells were suspended in the 50 uL serum-free DMEM medium, followed by being injected into the tail vein of nude mice.
Response Summary	In hepatocellular carcinoma, CASC11 decreased UBE2T N6-methyladenosine (m6A) level via recruiting ALKBH5. CASC11 inhibited the association between UBE2T mRNA and m6A reader protein YTHDF2.

Renal cell carcinoma [ICD-11: 2C90]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[95]
Responsed Disease	Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Response Summary	The m6A-demethylases ALKBH5 and FTO are dysregulated in clear cell renal cell carcinoma and could be used as prognostic biomarkers. ALKBH5 mRNA, as well as ALKBH5 and FTO protein expressions, was significantly downregulated in ccRCC compared to normal tissue and most of the other studied tumour entities.

Oral cavity/oesophagus/stomach in situ carcinoma [ICD-11: 2E60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[96]
Responsed Disease	Esophageal squamous cell carcinoma [ICD-11: 2B70.1]
In-vitro Model	TE-13	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_4463
	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
	HEK293T	Normal	Homo sapiens	CVCL_0063
	Eca-109	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898
Response Summary	The loss of ALKBH5 expression contributes to esophageal squamous cell carcinoma malignancy.

Lupus erythematosus [ICD-11: 4A40]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[97]
Responsed Disease	Lupus erythematosus [ICD-11: 4A40]
Response Summary	These findings suggested decreased YTHDF2 that was associated with disease activity play an important role in the pathogenesis of SLE, METTL14 and ALKBH5 were concomitantly decreased.

Ischemic heart disease [ICD-11: BA40-BA6Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[98]
Responsed Disease	Ischemic heart disease [ICD-11: BA40-BA6Z]
In-vitro Model	HL-1	Normal	Mus musculus	CVCL_0303
In-vivo Model	A total of 18 mice were randomly divided into 2 groups, a sham group (n=9), and a MIRI group (n=9). Operators were blinded to the allocation. The MIRI mice were established by ligation of the left anterior descending coronary artery. After peritoneal anesthesia with 1% pentobarbital sodium, surgical incisions were made between the third and fourth sternal intercostals to expose the heart. The left anterior descending coronary artery was identified under the microscope, and the left atrial appendage was ligated at the 1 cm lower margin with a suture needle to induce ischemia for 30 minutes. Then, the slip knot was unwound for 24 h of reperfusion. The sham group was not ligated. No unexpected adverse events were observed and animals were not excluded. Myocardium and peripheral blood were collected after the mice were sacrificed at 24 h reperfusion. Each group was analyzed in at least 3 independent experiments, which made the group size of each experiment 3.
Response Summary	The downregulated ALKBH5 contributes to myocardial ischemia/reperfusion injury(MIRI) process by increasing the m6A modification of Trio mRNA and downregulating Trio.

Liver disease [ICD-11: DB9Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[99]
Responsed Disease	Liver disease [ICD-11: DB9Z]
Pathway Response	PPAR signaling pathway	hsa03320
Cell Process	Fatty degeneration
In-vivo Model	A total of 24 male mice were randomly allocated to LFD (low-fat diet), LFDR (low-fat diet + resveratrol), HFD (high-fat diet), and HFDR (high-fat diet + resveratrol) groups for 12 weeks (n = 6/group).
Response Summary	The beneficial effect of resveratrol on lipid metabolism disorder under HFD is due to a decrease of m6A RNA methylation and an increase of PPARalpha mRNA, providing mechanistic insights into the function of resveratrol in alleviating the disturbance of lipid metabolism in mice. The resveratrol in HFD increased the transcript levels of methyltransferase like 3 (METTL3), alkB homolog 5 (ALKBH5), fat mass and obesity associated protein (FTO), and YTH domain family 2 (YTHDF2), whereas it decreased the level of YTH domain family 3 (YTHDF3) and m6A abundance in mice liver.

Menopausal disorder [ICD-11: GA30]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[100]
Responsed Disease	Premature ovarian failure [ICD-11: GA30.6]
Cell Process	Cell proliferation
	Cell apoptosis
In-vitro Model	Hgc (Primary human ovarian granulosa cells)
In-vivo Model	To build the mouse model for POI, cyclophosphamide (CTX) (Sigma, St. Louis, MO) was used a high-dose treatment (120 mg/kg, 2 weeks).
Response Summary	The decreased mRNA and protein expression levels of FTO are responsible for the increase in m6A in POI, which can further increase the risk of complications of POI. FACS was used to measure the levels of proliferation and apoptosis, and siRNA was used to establish FTO and ALKBH5 knockdown cell lines. The m6A content in the RNA from POI patients and POI mice was significantly higher than control groups and that POI was characterized by the content of m6A.

Male infertility [ICD-11: GB04]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[101]
Responsed Disease	Male infertility [ICD-11: GB04]
Responsed Drug	Ethyl ester form of meclofenamic acid		Approved	Drug Info
Cell Process	Cell cycle
	Cell proliferation
In-vitro Model	GC-1 spg	Normal	Mus musculus	CVCL_8872
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Mouse GC-1 spg cells were treated with the ester form of meclofenamic acid (MA2) to inhibit the demethylase activity of FTO.
Response Summary	METTL3, METTL14, ALKBH5 and YTHDC2 are involved in the regulation of spermatogenesis and oogenesis. MA2 affected CDKs expression through the m6A-dependent mRNA degradation pathway, and thus repressed spermatogonial proliferation. Additionally, mutation of the predicted m6A sites in the Cdk2-3'UTR could mitigated the degradation of CDK2 mRNA after MA2 treatment.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[102]
Responsed Disease	Arrest of spermatogenesis [ICD-11: GB04.Y]
In-vitro Model	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
Response Summary	A knockout of the Alkbh5 gene in mice resulted in impaired male fertility due to compromised spermatogenesis.

Bone morphogenetic protein 2 (BMP2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: 9.58E-01 p-value: 1.09E-02
More Results	Click to View More RNA-seq Results

MK22606 [Investigative]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[4]
Responsed Disease	Ossification of spinal ligaments	ICD-11: FA83	Disease Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway		hsa04151
Cell Process	Ossification
In-vitro Model	Ligamentum flavum cells (Ligamentum flavum cells)
Response Summary	The overexpression of ALKBH5 led to the activation of p-AKT, and Bone morphogenetic protein 2 (BMP2) was regulated by ALKBH5 through the AKT signaling pathway. ALKBH5 promoted the osteogenesis of the ligamentum flavum cells through BMP2 demethylation and AKT activation. MK22606 is an AKT inhibitor. Moreover, when ALKBH5 was knocked down in the ligamentum flavum cells, p-AKT was inhibited when compared with that in the overexpressed ALKBH5 and control groups.

Breast cancer type 1 susceptibility protein (BRCA1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	HaCAT cell line	Homo sapiens
Treatment: siALKBH5 HaCAT cells Control: siControl HaCAT cells		GSE211076
Regulation		logFC: 7.57E-01 p-value: 2.32E-06
More Results	Click to View More RNA-seq Results

Doxil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[5]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Up regulation
In-vitro Model	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	HCC1937	Breast ductal carcinoma	Homo sapiens	CVCL_0290
In-vivo Model	For the subcutaneously transplanted tumor model, wild-type, PRMT5-overexpressing or doxorubicin-resistant MDA-MB-231 cells (5 × 10⁶ per mouse, n = 5-7 for each group) were diluted in 100 uL of phosphate-buffered saline (PBS) plus 100 uL of Matrigel (BD Biosciences) and subcutaneously injected into female nude mice to investigate tumor growth. When all tumor volumes reached 100 mm³, the mice were randomly assigned and treated with the indicated drugs. In the experiment, doxorubicin was administered once a week via intravenous tail vein injection at 2 mg/kg body weight, and tadalafil was administered daily via oral gavage at 2 mg/kg body weight. Tumor volume was measured every 3 days using a digital caliper and calculated using the formula V = 1/2 × (diameter) × (smaller diameter)2. The mice were euthanized 27 days after injection.
Response Summary	ALKBH5 removed the m6A methylation of Breast cancer type 1 susceptibility protein (BRCA1) for mRNA stabilization and further enhanced DNA repair competency to decrease doxorubicin efficacy in breast cancer cells.

RAC-alpha serine/threonine-protein kinase (AKT1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: -9.73E-01 p-value: 3.10E-07
More Results	Click to View More RNA-seq Results

MK22606 [Investigative]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[4]
Responsed Disease	Ossification of spinal ligaments	ICD-11: FA83	Disease Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway		hsa04151
Cell Process	Ossification
In-vitro Model	Ligamentum flavum cells (Ligamentum flavum cells)
Response Summary	The overexpression of ALKBH5 led to the activation of RAC-alpha serine/threonine-protein kinase (AKT1), and BMP2 was regulated by ALKBH5 through the AKT signaling pathway. ALKBH5 promoted the osteogenesis of the ligamentum flavum cells through BMP2 demethylation and AKT activation. MK22606 is an AKT inhibitor. Moreover, when ALKBH5 was knocked down in the ligamentum flavum cells, p-AKT was inhibited when compared with that in the overexpressed ALKBH5 and control groups.

Tyrosine-protein kinase JAK2 (JAK2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	NOMO-1 cell line	Homo sapiens
Treatment: shALKBH5 NOMO-1 cells Control: shNS NOMO-1 cells		GSE144968
Regulation		logFC: 1.17E+00 p-value: 2.74E-05
More Results	Click to View More RNA-seq Results

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[52]
Responsed Disease	Malignant mixed epithelial mesenchymal tumour of ovary		ICD-11: 2B5D.0	Disease Info
Target Regulation	Up regulation
Pathway Response	JAK-STAT signaling pathway			hsa04630
In-vitro Model	HO8910-DDP (HO8910 underwent continuous stepwise exposure to increasing concentrations of cisplatin to create the cisplatin-resistant cell lines HO8910-DDP)
	HO-8910	Endocervical adenocarcinoma	Homo sapiens	CVCL_6868
	A2780-DDP (A2780 underwent continuous stepwise exposure to increasing concentrations of cisplatin to create the cisplatin-resistant cell line)
	A2780	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
In-vivo Model	About 5× 10⁶ cells were injected subcutaneously into the axilla of the female athymic BALB/C nude mice (4 week-old, 18-20?g). When the average tumor size reached approximately 100mm³ (after 1 week), mice were then randomized into two groups and treated with cisplatin (5 mg/kg) or normal saline (NS) weekly.
Response Summary	The ALKBH5-HOXA10 loop jointly activates the JAK2/STAT3 signaling pathway by mediating Tyrosine-protein kinase JAK2 (JAK2) m6A demethylation, promoting epithelial ovarian cancer resistance to cisplatin.

Ubiquitin carboxyl-terminal hydrolase 1 (USP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	143B cell line	Homo sapiens
Treatment: siALKBH5 transfected 143B cells Control: siControl 143B cells		GSE154528
Regulation		logFC: -6.03E-01 p-value: 1.12E-02
More Results	Click to View More RNA-seq Results

dexamethasone [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[54]
Responsed Disease	Mature T-cell lymphoma		ICD-11: 2A90	Disease Info
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	CEM/C1	T acute lymphoblastic leukemia	Homo sapiens	CVCL_3496
	CCRF-CEM C7	T acute lymphoblastic leukemia	Homo sapiens	CVCL_6825
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Adult male C57BL/6J mice (weighting 18-25 g) were obtained from Laboratory Animal Center, Zhengzhou University. Mice were subcutaneously injected with 1 × 10⁷ CEM-C1 cells for tumorigenesis and randomly divided into four group: control group; control + Dex; sh-RNA + Dex; sh-USP1 + Dex. Mice treatment with Dex were intraperitoneally injected with 8 mg/kg Dex every day for 10 consecutive days after tumor growth and mice treatment with sh-RNA or sh-USP1 were injected intravenously with 2 mg/Kg sh-RNA or USP1 sh-RNA. The control group of mice were injected with the same volume of normal saline. After the treatment of each group, the mice were housed and fed in a room with an ambient temperature of 25℃, and the survival time, weight of the mice, and tumor weight were recorded. When rats were sacrificed, tissues were harvested for Western blot analysis.
Response Summary	ALKBH5 and Ubiquitin carboxyl-terminal hydrolase 1 (USP1) were upregulated in T-cell acute lymphoblastic leukemia, and ALKBH5-mediated m6A modification increased USP1 and Aurora B expression. Silencing USP1 increased CEM-C1 cell sensitivity to dexamethasone, reduced cell invasion, promoted cell apoptosis, and ameliorated glucocorticoid receptor (GR) expression.

Glucocorticoid [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[54]
Responsed Disease	Mature T-cell lymphoma		ICD-11: 2A90	Disease Info
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	CEM/C1	T acute lymphoblastic leukemia	Homo sapiens	CVCL_3496
	CCRF-CEM C7	T acute lymphoblastic leukemia	Homo sapiens	CVCL_6825
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Adult male C57BL/6J mice (weighting 18-25 g) were obtained from Laboratory Animal Center, Zhengzhou University. Mice were subcutaneously injected with 1 × 10⁷ CEM-C1 cells for tumorigenesis and randomly divided into four group: control group; control + Dex; sh-RNA + Dex; sh-USP1 + Dex. Mice treatment with Dex were intraperitoneally injected with 8 mg/kg Dex every day for 10 consecutive days after tumor growth and mice treatment with sh-RNA or sh-USP1 were injected intravenously with 2 mg/Kg sh-RNA or USP1 sh-RNA. The control group of mice were injected with the same volume of normal saline. After the treatment of each group, the mice were housed and fed in a room with an ambient temperature of 25℃, and the survival time, weight of the mice, and tumor weight were recorded. When rats were sacrificed, tissues were harvested for Western blot analysis.
Response Summary	ALKBH5 and Ubiquitin carboxyl-terminal hydrolase 1 (USP1) were upregulated in T-cell acute lymphoblastic leukemia, and ALKBH5-mediated m6A modification increased USP1 and Aurora B expression. Silencing USP1 increased CEM-C1 cell sensitivity to dexamethasone, reduced cell invasion, promoted cell apoptosis, and ameliorated glucocorticoid receptor (GR) expression.

Casein kinase II subunit alpha' (CSNK2A2)

Target Gene

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[65]
Responsed Disease	Bladder cancer		ICD-11: 2C94	Disease Info
Target Regulation	Down regulation
Pathway Response	Metabolic pathways			hsa01100
Pathway Response	Glycolysis / Gluconeogenesis			hsa00010)
Cell Process	Glycolysis
In-vitro Model	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	J82	Bladder carcinoma	Homo sapiens	CVCL_0359
	253J	Bladder carcinoma	Homo sapiens	CVCL_7935
	5637	Bladder carcinoma	Homo sapiens	CVCL_0126
Response Summary	knockdown of ALKBH5 promoted bladder cancer cell proliferation, migration, invasion, and decreased cisplatin chemosensitivity, ALKBH5 inhibited the progression and sensitized bladder cancer cells to cisplatin through a Casein kinase II subunit alpha' (CSNK2A2)-mediated glycolysis pathway in an m6A-dependent manner.

Frizzled-10 (FZD10)

Target Gene

PARPi [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[69]
Responsed Disease	Malignant mixed epithelial mesenchymal tumour of ovary		ICD-11: 2B5D.0	Disease Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
In-vitro Model	UWB1.289	Ovarian carcinoma	Homo sapiens	CVCL_B079
In-vitro Model	PEO1	Ovarian cystadenocarcinoma	Homo sapiens	CVCL_2686
In-vivo Model	2 × 10⁷ PARP inhibitor resistant PEO1 cells were suspended in 200 uL PBS : Matrigel (1:1) unilaterally injected subcutaneously into the right dorsal flank of 6-8 week-old female immunocompromised non-obese diabetic/severe combined immunodeficiency (NOD/SCID) gamma (NSG) mice. When the average tumor size reached ~100 mm3, the mice were then randomized into four groups and treated with vehicle control, Olaparib (50 mg/kg), XAV939 (5 mg/kg) or a combination daily for 18 days.
Response Summary	Downregulation of m6A demethylases FTO and ALKBH5 was sufficient to increase Frizzled-10 (FZD10) mRNA m6A modification and reduce PARPi sensitivity, the finding elucidates a novel regulatory mechanism of PARPi resistance in EOC by showing that m6A modification of FZD10 mRNA contributes to PARPi resistance in BRCA-deficient EOC cells via upregulation of Wnt/Bete-catenin pathway.

Homeobox protein NANOG (NANOG)

Target Gene

Temozolomide [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[71]
Responsed Disease	Glioma		ICD-11: 2A00.0	Disease Info
Target Regulation	Up regulation
Cell Process	Cellular Processes
	Cell growth and death
	Cell apoptosis
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	U251 (Fibroblasts or fibroblast like cells)
	U87 (A primary glioblastoma cell line)
In-vivo Model	U251/TR cells (2 × 10⁶ per mouse) with stable transfection of sh-circ_0072083 or sh-NC were subcutaneously injected into mice.
Response Summary	In glioma, hsa_circ_0072083 could regulate Homeobox protein NANOG (NANOG) and ALKBH5 via targeting miR-1252-5p to control temozolomide resistance. circ_0072083 silence reduced NANOG expression via blocking ALKBH5-mediated demethylation.

Wnt inhibitory factor 1 (WIF1)

Target Gene

Gemcitabine [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[79]
Responsed Disease	Pancreatic cancer		ICD-11: 2C10	Disease Info
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
In-vitro Model	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	Capan-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0237
	Capan-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0026
	CFPAC-1	Cystic fibrosis	Homo sapiens	CVCL_1119
	HPDE6c7	Normal	Homo sapiens	CVCL_0P38
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
Response Summary	ALKBH5 overexpression sensitizes Pancreatic cancer cells to gemcitabine treatment, and it represses PDAC tumorigenesis by reducing m6A levels of Wnt inhibitory factor 1 (WIF1) and hindering activation of Wnt signaling.

Unspecific Target Gene

Ethyl ester form of meclofenamic acid [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[101]
Responsed Disease	Male infertility		ICD-11: GB04	Disease Info
Cell Process	Cell cycle
	Cell proliferation
In-vitro Model	GC-1 spg	Normal	Mus musculus	CVCL_8872
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Mouse GC-1 spg cells were treated with the ester form of meclofenamic acid (MA2) to inhibit the demethylase activity of FTO.
Response Summary	METTL3, METTL14, ALKBH5 and YTHDC2 are involved in the regulation of spermatogenesis and oogenesis. MA2 affected CDKs expression through the m6A-dependent mRNA degradation pathway, and thus repressed spermatogonial proliferation. Additionally, mutation of the predicted m6A sites in the Cdk2-3'UTR could mitigated the degradation of CDK2 mRNA after MA2 treatment.

Click to View Potential Drug Response of This Regulator

Xenobiotics Compound(s) Regulating the m6A Methylation Regulator

Compound Name	MPV 1440	Approved
Synonyms	Dexmedetomidina; Dexmedetomidinum; MPV 1440; MPV-1440; Precedex (TN); Dexmedetomidine (USAN/INN); (+)-4-((S)-alpha,2,3-Trimethylbenzyl)imidazole; 4-[(1S)-1-(2,3-dimethylphenyl)ethyl]-1H-imidazole; 5-[(1S)-1-(2,3-dimethylphenyl)ethyl]-1H-imidazole Click to Show/Hide
External link	CID: 5311068 TTD: D0U3DU DrugBank: DB00633
Description	ALKBH5 could up-regulateMALAT1 expression by demethylation. Furthermore, dexmedetomidine inhibited the expression of ALKBH5 in LPS-treated HK-2 cells. Dexmedetomidine suppressed the biological behavior of HK-2 cells treated with LPS by inhibiting the expression of ALKBH5 in vitro, which provides potential targets for the prevention and treatment of sepsis-induced kidney injury. Dexmedetomidine suppressed the biological behavior of HK-2 cells treated with LPS by inhibiting the expression of ALKBH5 in vitro, which provides potential targets for the prevention and treatment ofsepsis-induced kidney injury.	[57]
Compound Name	Citric acid	Investigative
Synonyms	citric acid; 77-92-9; 2-hydroxypropane-1,2,3-tricarboxylic acid; Citric acid, anhydrous; Anhydrous citric acid; Citro; Aciletten; Citretten; Chemfill; Hydrocerol A; 1,2,3-Propanetricarboxylic acid, 2-hydroxy-; 2-hydroxy-1,2,3-propanetricarboxylic acid; Citric acid anhydrous; Kyselina citronova; 2-Hydroxytricarballylic acid; Caswell No. 221C; F 0001 (polycarboxylic acid); 3-Carboxy-3-hydroxypentane-1,5-dioic acid; 2-Hydroxypropanetricarboxylic acid; FEMA No. 2306; FEMA Number 2306; K-Lyte; Kyselina citronova [Czech]; K-Lyte DS; CCRIS 3292; HSDB 911; EPA Pesticide Chemical Code 021801; Uro-trainer; AI3-06286; UNII-XF417D3PSL; Suby G; NSC 30279; NSC 626579; BRN 0782061; Citric acid,anhydrous; MFCD00011669; CHEMBL1261; XF417D3PSL; Kyselina 2-hydroxy-1,2,3-propantrikarbonova [Czech]; Kyselina 2-hydroxy-1,2,3-propantrikarbonova; CHEBI:30769; .beta.-Hydroxytricarballylic acid; citr; NSC30279; NSC-30279; NSC626579; NSC-626579; Citric acid, 99%; NCGC00090954-03; E330; DSSTox_CID_332; E 330; beta-Hydroxytricarballylic acid; CITRATE ANION; DSSTox_RID_75520; DSSTox_GSID_20332; 1,2,3-Propanetricarboxylic acid, 2-hydroxy-, homopolymer; Citric acid [USAN:JAN]; CAS-77-92-9; 141633-96-7; 1,3-Propanetricarboxylic acid, 2-hydroxy-; NSC-112226; EINECS 201-069-1; Citraclean; Citronensaeure; Acidum citricum; citric-acid; Citricum acidum; Citric acid bp; Anhydrous citrate; 2fwp; 4aci; 4nrm; H3cit; Citric acid, anhydrous [USP:JAN]; Citric acid,hydrous; Citric Acid,(S); Citric acid, hydrous; Citric acid (8CI); K-Lyte (Salt/Mix); 1i2s; 1o4l; 1rq2; 1y4a; 2bo4; 2c4v; 2fw6; 4to8; Citraclean (Salt/Mix); Citric acid-[13C6]; Citric Acid (Anhydrous); 10402-15-0; Spectrum3_001850; WLN: QV1XQVQ1VQ; beta-Hydroxytricarballylate; cid_311; K-Lyte/Cl (Salt/Mix); K-Lyte DS (Salt/Mix); Acidum citricum monohydrate; bmse000076; HOC(CH2COOH)2COOH; EC 201-069-1; NCIStruc1_000057; NCIStruc2_000099; NCIOpen2_004062; NCIOpen2_004502; Oprea1_502996; BSPBio_003240; Citric acid anhydrous (JAN); 4-03-00-01272 (Beilstein Handbook Reference); Citric Acid, anhydrous, USP; MLS001066346; citric acid (Fragrance Grade); Citric acid, anhydrous (USP); Anhydrous citric acid (JP17); GTPL2478; INS NO.330; Citric Acid (Industrial Grade); Citric acid, analytical standard; DTXSID3020332; BDBM14672; Citric acid, p.a., 99.5%; KBio3_002740; INS-330; 4o61; Citric acid 5% solution in water; Citric acid, Electrophoresis Grade; HMS1787N01; HMS2268B04; Pharmakon1600-01300013; ZINC895081; Citric acid 10% solution in water; HY-N1428; STR12052; 1,2,3-Tricarboxy-2-hydroxypropane; Tox21_113436; Tox21_202405; Tox21_300124; BBL002530; NSC759606; s5761; STK286098; AKOS000119911; Citric acid, LR, anhydrous, >=99%; 2-hydroxy-1,2,3-propanetricarboxylate; CS-6965; DB04272; MCULE-7981253226; NSC-759606; 3-Carboxy-3-hydroxypentane-1,5-dioate; Citric acid, >=99.5%, FCC, FG; Citric acid, ACS reagent, >=99.5%; Citric Acid, anhydrous powder, A.C.S.; 2-Hydroxy-1,3-propanetricarboxylic acid; NCGC00090954-01; NCGC00090954-02; NCGC00090954-04; NCGC00090954-05; NCGC00254055-01; NCGC00259954-01; BP-31028; Citric Acid, anhydrous granular, A.C.S.; NCI60_022579; SMR000471840; 2-hydroxy-1,2,3-propanetricarboxyic acid; Citric acid 50% solution in water (w/w); SBI-0206765.P001; Citric acid, SAJ first grade, >=99.5%; 2-Hydroxy-1,2,3-propane tricarboxylic acid; 2-Hydroxy-1,2,3-propanenetricarboxylic acid; B7297; C1949; Citric Acid, Aqueous Solution (Food Grade); Citric acid, Vetec(TM) reagent grade, 99%; E-330; FT-0623957; FT-0665073; FT-0728530; C00158; D00037; AE-562/40806920; Citric acid, BioUltra, anhydrous, >=99.5% (T); Q159683; J-520099; 1,2,3-Propanetricarboxylic acid, 2-hydroxy- (9CI); Z56754862; Citric acid (monohydrate): H2O = 1 g : 1 ml solution; Citric acid, certified reference material, TraceCERT(R); Citric acid, meets USP testing specifications, anhydrous; F2191-0222; 8F5D336A-442D-434A-9FB0-E400FF74E343; Citrate standard for IC, 1000 mg/L, analytical standard; 1,2,3-PROPANETRICARBOXYLIC ACID,2-HYDROXY (CITRIC ACID); Citric acid, United States Pharmacopeia (USP) Reference Standard; Citric acid, anhydrous, cell culture tested, plant cell culture tested; Citric acid, anhydrous, European Pharmacopoeia (EP) Reference Standard; Citric acid, anhydrous, free-flowing, Redi-Dri(TM), ACS reagent, >=99.5%; Citric acid, Anhydrous, Pharmaceutical Secondary Standard; Certified Reference Material; Citric acid, meets analytical specification of Ph. Eur., BP, USP, E330, anhydrous, 99.5-100.5% (based on anhydrous substance) Click to Show/Hide
External link	CID: 311
Activity	IC50 = 488000 nM	[104]
Compound Name	IOX1	Investigative
Synonyms	5852-78-8; 8-Hydroxyquinoline-5-Carboxylic Acid; 8-Hydroxy-5-quinolinecarboxylic acid; 5-Carboxy-8-hydroxyquinoline; IOX 1; UNII-JM015YQC1C; IOX-1; 5-carboxy-8HQ; 5-Quinolinecarboxylic acid, 8-hydroxy-; JM015YQC1C; CHEMBL1230640; 4bio; 4jht; 8XQ; 4ie4; AC1LA0UV; MLS002729056; GTPL8230; SCHEMBL6068195; KS-00000PPH; CHEBI:93239; CTK1E0142; DTXSID20207236; AOB6499; JGRPKOGHYBAVMW-UHFFFAOYSA-N; MolPort-006-673-354; HMS3653E21; ZINC5933707; BCP16996; s7234; BDBM50396018; 2184AH; IOX1, > AKOS016371793 Click to Show/Hide
External link	CID: 459617 TTD: D0X5US
Description	IOX1, which is an inhibitor of ALKBH5, was loaded on HSSS to form HSSS-I, which could effectively ameliorate cardiac dysfunction inacute myocardial infarction. The surface-modified bioengineered ferritin nanocage targeted the dying cells in the infarct area under the guidance ofScarf1. These cells were then phagocytosed through recognition of their TfR1 receptor.	[38]

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m6A Regulator Information

Cite M6AREG

Correspondence

Prof. Feng ZHU

Prof. Shuiping Liu

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