Name	Head and neck squamous carcinoma
ICD	ICD-11: 2B6E

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	FTO expression was significantly upregulated in HNSCC datasets and tissues. FTO expression was significantly correlated with Catenin beta-1 (CTNNB1/Beta-catenin) expression. Moreover, it exerted a tumorigenic effect by increasing CTNNB1 expression in an m6A-dependent manner.
Responsed Disease	Head and neck squamous carcinoma [ICD-11: 2B6E]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Adherens junction			hsa04520
Cell Process	Cell proliferation and migration
In-vitro Model	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107
	FaDu	Hypopharyngeal squamous cell carcinoma	Homo sapiens	CVCL_1218
	Tu 686	Laryngeal squamous cell carcinoma	Homo sapiens	CVCL_4916
	HN-6	Tongue squamous cell carcinoma	Homo sapiens	CVCL_8129
	HEp-2	Endocervical adenocarcinoma	Homo sapiens	CVCL_1906

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	The study identified the mechanism by which rapamycin affects autophagy via regulating METTL14, which provides a new idea for a potential targeted therapy for oral squamous cell carcinoma. METTL14 mediated Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) expression via m6A modification and regulated autophagy levels and biological functions in oral squamous cell carcinoma.
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cell autophagy
In-vitro Model	CAL-33	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1108
	HN-6	Tongue squamous cell carcinoma	Homo sapiens	CVCL_8129
	HSC-3	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1288
In-vivo Model	Specific pathogen-free (SPF) female NOD/SCID mice (5-6 weeks old) were randomly distributed into two groups: the OECtrl group and the OEMETTL14 groups. Phosphate buffer (200 uL) containing approximately 5 × 107 HSC3 or CAL33 cells was subcutaneously injected into the inner thigh of each mouse. The mice were euthanized two weeks after injection, and the tumour xenografts were harvested, photographed, weighed, and fixed.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	Rapamycin inhibited FTO activity, and directly targeted Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) transcripts and mediated their expression in an m6A-dependent manner in oral squamous cell carcinoma. After FTO silencing, YTHDF2 captured eIF4G1 transcripts containing m6A, resulting in mRNA degradation and decreased expression of eIF4G1 protein, thereby promoting autophagy and reducing tumor occurrence.
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cell autophagy
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	Rapamycin inhibited FTO activity, and directly targeted Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) transcripts and mediated their expression in an m6A-dependent manner in oral squamous cell carcinoma. After FTO silencing, YTHDF2 captured eIF4G1 transcripts containing m6A, resulting in mRNA degradation and decreased expression of eIF4G1 protein, thereby promoting autophagy and reducing tumor occurrence.
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cell autophagy

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	METTL3 enhanced the m6A modification of M-phase inducer phosphatase 2 (CDC25B) mRNA, which maintained its stability and upregulated its expression, thereby activating G2/M phase of cell cycle and leading to HNSCC malignant progression.
Responsed Disease	Head and neck squamous carcinoma [ICD-11: 2B6E]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	Tu 686	Laryngeal squamous cell carcinoma	Homo sapiens	CVCL_4916
	Tu 212	Head and neck squamous cell carcinoma	Homo sapiens	CVCL_4915
	SAS	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1675
	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	HEp-2	Endocervical adenocarcinoma	Homo sapiens	CVCL_1906
	FaDu	Hypopharyngeal squamous cell carcinoma	Homo sapiens	CVCL_1218
In-vivo Model	Tumour xenograft models were established in nude mice bearing: SAS cells cells stably transfected with METTL3-shRNA and the corresponding control vector. The different HNSCC cells (5 × 106) were subcutaneously injected into the right axilla of nude mice (n = 6 per group).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	High METTL3 expression was positively correlated with more severe clinical features of OSCC tumors. Furthermore, METTL3-KD and cycloleucine, a methylation inhibitor, decreased m6A levels and down-regulated Mitogen-activated protein kinase 14 (p38/MAPK14) expression in OSCC cells.
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	SCC-25	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1682
	SCC-15	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1681
In-vivo Model	Male BALB/c-nu/nu mice, 9-10 weeks of age, were acclimatized for a week prior to the experiments. Nude mice (6 each group) were subcutaneously inoculated with 4 × 106 SCC-25 or SCC-15 cells through an injection into the center of the back, which consistently caused tumor formation within 1 week of inoculation. To monitor the initial tumor appearance, animals were observed every day. After tumor appeared, measurements were made every week with a caliper. After 28 days, mice were sacrificed and tumors were dissected out to be weighed.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	HNRNPA2B1, as an m6A reader, is critical in OSCC development. Its expression is significantly associated with the prognosis of Oral Squamous Cell Carcinoma(OSCC). m6A acts as a proto-oncogene that promotes the OSCC proliferation, migration, and invasion through the EMT progression via the LINE-1/TGF-beta1/Snail/Mothers against decapentaplegic homolog 2 (SMAD2) signaling pathway.
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
In-vitro Model	SCC-4	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1684
	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	In oral squamous cell carcinoma, YTH N6-methyladenosine RNA binding protein 1 (YTH domain family, member 1 [YTHDF1]) mediated the m6A-increased stability of Myc proto-oncogene protein (MYC) mRNA catalyzed by METTL3.
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	RNA stability
In-vitro Model	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107
	NHOK (Normal oral keratinocytes)
	SCC-15	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1681
	SCC-25	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1682
	TSCCa	Endocervical adenocarcinoma	Homo sapiens	CVCL_VL15
In-vivo Model	The stable transfection of SCC25 cells (1 × 107 cells in 0.1 mL) with lenti-sh-METTL3 or blank vectors was injected subcutaneously into BALB/c nude mice.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	In oral squamous cell carcinoma, YTH N6-methyladenosine RNA binding protein 1 (YTH domain family, member 1 [YTHDF1]) mediated the m6A-increased stability of Myc proto-oncogene protein (MYC) mRNA catalyzed by METTL3.
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	RNA stability
In-vitro Model	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107
	NHOK (Normal oral keratinocytes)
	SCC-15	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1681
	SCC-25	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1682
	TSCCa	Endocervical adenocarcinoma	Homo sapiens	CVCL_VL15
In-vivo Model	The stable transfection of SCC25 cells (1 × 107 cells in 0.1 mL) with lenti-sh-METTL3 or blank vectors was injected subcutaneously into BALB/c nude mice.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	METTL3 promotes Polycomb complex protein BMI-1 (BMI1) translation in OSCC under the cooperation with m6A reader IGF2BP1. And the study revealed that METTL3 promotes OSCC proliferation and metastasis through BMI1 m6A methylation.
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	UM1	Tongue squamous cell carcinoma	Homo sapiens	CVCL_VH00
	SCC-9	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1685
	SCC-25	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1682
	SCC-15	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1681
	HSC-3	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1288
	HOK	Normal	Hexagrammos otakii	CVCL_YE19
In-vivo Model	To construct the subcutaneous tumorigenesis model, the cells were suspended in 100 uL of PBS and Matrigel matrix (BD Biosciences, USA) (1:1) and injected into the right flanks of 6-week-old female BALB/c nude mice.To construct the lymph node metastasis model, we injected 1 × 105/50 uL stably infected SCC9 cells into the left hind footpads of BALB/c mice.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	METTL3 promotes Polycomb complex protein BMI-1 (BMI1) translation in OSCC under the cooperation with m6A reader IGF2BP1. And the study revealed that METTL3 promotes OSCC proliferation and metastasis through BMI1 m6A methylation.
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	UM1	Tongue squamous cell carcinoma	Homo sapiens	CVCL_VH00
	SCC-9	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1685
	SCC-25	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1682
	SCC-15	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1681
	HSC-3	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1288
	HOK	Normal	Hexagrammos otakii	CVCL_YE19
In-vivo Model	To construct the subcutaneous tumorigenesis model, the cells were suspended in 100 uL of PBS and Matrigel matrix (BD Biosciences, USA) (1:1) and injected into the right flanks of 6-week-old female BALB/c nude mice.To construct the lymph node metastasis model, we injected 1 × 105/50 uL stably infected SCC9 cells into the left hind footpads of BALB/c mice.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[9]
Response Summary	METTL3 intensified the metastasis and proliferation of OSCC by modulating the m6A amounts of PRMT5 and Programmed cell death 1 ligand 1 (CD274/PD-L1).
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
In-vitro Model	SCC-9	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1685
	SCC-4	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1684
	SCC-25	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1682
	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107
In-vivo Model	Six-week-old nude mice were randomly divided into two groups (three mice per group) and cultured with continuous access to sterile food and water in pathogen-free sterile conditions. To establish the OSCC xenograft model, we subcutaneously injected 5 × 106 SCC-9 cells stably transfected with METTL3 shRNA or sh-NC vectors into nude mice.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[10]
Response Summary	Arecoline-induced FTO promotes the stability and expression levels of Programmed cell death 1 ligand 1 (CD274/PD-L1) transcripts through mediating m6A modification and MYC activity, respectively. PD-L1 upregulation confers superior cell proliferation, migration, and resistance to T-cell killing to OSCC cells.
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[9]
Response Summary	METTL3 intensified the metastasis and proliferation of OSCC by modulating the m6A amounts of Protein arginine N-methyltransferase 5 (PRMT5) and PD-L1.
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
In-vitro Model	SCC-9	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1685
	SCC-4	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1684
	SCC-25	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1682
	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107
In-vivo Model	Six-week-old nude mice were randomly divided into two groups (three mice per group) and cultured with continuous access to sterile food and water in pathogen-free sterile conditions. To establish the OSCC xenograft model, we subcutaneously injected 5 × 106 SCC-9 cells stably transfected with METTL3 shRNA or sh-NC vectors into nude mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[11]
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.
Responsed Disease	Head and neck squamous carcinoma [ICD-11: 2B6E]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
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).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	Stable knockdown of FTO inhibited OSCC cell viability, colony formation, and tumor growth. Further, FTO depletion increased Transcriptional coactivator YAP1 (YAP1) m6A modification at mRNA 3'-untranslated region, accelerating the degradation of YAP1 mRNA, a well-documented oncogene promoting OSCC progression.
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	HNRNPA2B1, as an m6A reader, is critical in OSCC development. Its expression is significantly associated with the prognosis of Oral Squamous Cell Carcinoma(OSCC). m6A acts as a proto-oncogene that promotes the OSCC proliferation, migration, and invasion through the EMT progression via the LINE-1/Transforming growth factor beta-1 proprotein (TGFB1)/Snail/Smad2 signaling pathway.
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
In-vitro Model	SCC-4	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1684
	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	HNRNPA2B1, as an m6A reader, is critical in OSCC development. Its expression is significantly associated with the prognosis of Oral Squamous Cell Carcinoma(OSCC). m6A acts as a proto-oncogene that promotes the OSCC proliferation, migration, and invasion through the EMT progression via the LINE-1/TGF-beta1/Zinc finger protein SNAI1 (SNAI1)/Smad2 signaling pathway.
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
In-vitro Model	SCC-4	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1684
	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[13]
Response Summary	Mechanistic investigations revealed that Zinc finger protein SNAI2 (Slug), a key EMT-related transcriptional factor, is the direct target of IGF2BP2, and essential for IGF2BP2-regulated EMT and metastasis in HNSCC.
Responsed Disease	Head and neck squamous carcinoma [ICD-11: 2B6E]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Adherens junction			hsa04520
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	SCC-15	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1681
	FaDu	Hypopharyngeal squamous cell carcinoma	Homo sapiens	CVCL_1218
In-vivo Model	To construct the metastasis model, 5 × 106 FaDu cells were transfected with sh-IGF2BP2-luc and sh-NC-luc, suspended in 60 uL PBS, and then injected into the footpads of the mice. Six weeks after injection, mice were subjected to bioluminescence imaging to evaluate lymphatic metastasis. For bioluminescence imaging, mice were anesthetized by inhaling 2% isoflurane for approximately 5 min, injected intraperitoneally with D-Luciferin potassium salt (200 uL, 150 ug/ml, ST196, Beyotime, Shanghai, China), and imaged with a bioluminescence system (NightOwl II LB983, Berthold Technologies, Germany).

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[14]
Response Summary	The N6-methyladenosine (m6A) modification mediated by METTL3 and METTL14 enhanced the stability of LncRNA activating regulator of DKK1 (LNCAROD) in head and neck squamous cell carcinoma cells. LNCAROD is stabilized by m6A methylation and promotes cancer progression via forming a ternary complex with HSPA1A and YBX1 in head and neck squamous cell carcinoma.
Responsed Disease	Head and neck squamous carcinoma [ICD-11: 2B6E]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Proteasome			hsa03050
Cell Process	Proteasomal degradation
In-vitro Model	C666-1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_7949
	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107
	FaDu	Hypopharyngeal squamous cell carcinoma	Homo sapiens	CVCL_1218
	HK1	Nasopharyngeal carcinoma	Acipenser baerii	CVCL_YE27
	NP69 (A human immortalized nasopharyngeal epithelial)
	Tca8113	Endocervical adenocarcinoma	Homo sapiens	CVCL_6851
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[14]
Response Summary	The N6-methyladenosine (m6A) modification mediated by METTL3 and METTL14 enhanced the stability of LncRNA activating regulator of DKK1 (LNCAROD) in head and neck squamous cell carcinoma cells. LNCAROD is stabilized by m6A methylation and promotes cancer progression via forming a ternary complex with HSPA1A and YBX1 in head and neck squamous cell carcinoma.
Responsed Disease	Head and neck squamous carcinoma [ICD-11: 2B6E]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Proteasome			hsa03050
Cell Process	Proteasomal degradation
In-vitro Model	C666-1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_7949
	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107
	FaDu	Hypopharyngeal squamous cell carcinoma	Homo sapiens	CVCL_1218
	HK1	Nasopharyngeal carcinoma	Acipenser baerii	CVCL_YE27
	NP69 (A human immortalized nasopharyngeal epithelial)
	Tca8113	Endocervical adenocarcinoma	Homo sapiens	CVCL_6851

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[15]
Response Summary	METTL14 and lncRNA Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) were upregulated, and miR-224-5p was downregulated in OSCC tissues and cells. METTL14 induced m6A modification of MALAT1 to upregulate MALAT1.
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	SCC-25	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1682
	SCC-15	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1681
	Hs 680.Tg	Normal	Homo sapiens	CVCL_0842
	FaDu	Hypopharyngeal squamous cell carcinoma	Homo sapiens	CVCL_1218
	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107
In-vivo Model	Lentiviruses containing sh-METTL-14 and its negative control (RiboBio Co., Ltd., Guangzhou, China) were transduced into CAL27 cells and stably transduced cells were screened using puromycin. CAL27 cells (3 × 106 cells/mouse) were subcutaneously inoculated into the posterior flank of each mouse (N = 12/group).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	HNRNPA2B1, as an m6A reader, is critical in OSCC development. Its expression is significantly associated with the prognosis of Oral Squamous Cell Carcinoma(OSCC). m6A acts as a proto-oncogene that promotes the OSCC proliferation, migration, and invasion through the EMT progression via the LINE-1 (LINE-1)/TGF-beta1/Snail/Smad2 signaling pathway.
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
In-vitro Model	SCC-4	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1684
	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107

Ref 1	The RNA N6-Methyladenosine Demethylase FTO Promotes Head and Neck Squamous Cell Carcinoma Proliferation and Migration by Increasing CTNNB1. Int J Gen Med. 2021 Nov 24;14:8785-8795. doi: 10.2147/IJGM.S339095. eCollection 2021.
Ref 2	N6-Methyladenosine Methyltransferase METTL14-Mediated Autophagy in Malignant Development of Oral Squamous Cell Carcinoma. Front Oncol. 2021 Nov 24;11:738406. doi: 10.3389/fonc.2021.738406. eCollection 2021.
Ref 3	N6-methyladenosine demethyltransferase FTO-mediated autophagy in malignant development of oral squamous cell carcinoma. Oncogene. 2021 Jun;40(22):3885-3898. doi: 10.1038/s41388-021-01820-7. Epub 2021 May 10.
Ref 4	METTL3 modulates m6A modification of CDC25B and promotes head and neck squamous cell carcinoma malignant progression. Exp Hematol Oncol. 2022 Mar 14;11(1):14. doi: 10.1186/s40164-022-00256-3.
Ref 5	Methyltransferase-like 3-induced N6-methyladenosine upregulation promotes oral squamous cell carcinoma by through p38. Oral Dis. 2021 Sep 3. doi: 10.1111/odi.14016. Online ahead of print.
Ref 6	HNRNPA2B1, as a m(6)A Reader, Promotes Tumorigenesis and Metastasis of Oral Squamous Cell Carcinoma. Front Oncol. 2021 Sep 23;11:716921. doi: 10.3389/fonc.2021.716921. eCollection 2021.
Ref 7	METTL3 Facilitates Oral Squamous Cell Carcinoma Tumorigenesis by Enhancing c-Myc Stability via YTHDF1-Mediated m(6)A Modification. Mol Ther Nucleic Acids. 2020 Jun 5;20:1-12. doi: 10.1016/j.omtn.2020.01.033. Epub 2020 Feb 4.
Ref 8	METTL3 Promotes Tumorigenesis and Metastasis through BMI1 m(6)A Methylation in Oral Squamous Cell Carcinoma. Mol Ther. 2020 Oct 7;28(10):2177-2190. doi: 10.1016/j.ymthe.2020.06.024. Epub 2020 Jun 24.
Ref 9	METTL3 Intensifies the Progress of Oral Squamous Cell Carcinoma via Modulating the m6A Amount of PRMT5 and PD-L1. J Immunol Res. 2021 Aug 23;2021:6149558. doi: 10.1155/2021/6149558. eCollection 2021.
Ref 10	Fat mass and obesity-associated protein regulates arecoline-exposed oral cancer immune response through programmed cell death-ligand 1. Cancer Sci. 2022 Mar 15. doi: 10.1111/cas.15332. Online ahead of print.
Ref 11	The m6A demethylase ALKBH5 promotes tumor progression by inhibiting RIG-I expression and interferon alpha production through the IKKEpsilon/TBK1/IRF3 pathway in head and neck squamous cell carcinoma. Mol Cancer. 2022 Apr 9;21(1):97. doi: 10.1186/s12943-022-01572-2.
Ref 12	FTO demethylates YAP mRNA promoting oral squamous cell carcinoma tumorigenesis. Neoplasma. 2022 Jan;69(1):71-79. doi: 10.4149/neo_2021_210716N967. Epub 2021 Nov 16.
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