Name	Osteosarcoma
ICD	ICD-11: 2B51

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	METTL3 functions as an oncogene in the growth and invasion of osteosarcoma by regulating ATPase family AAA domain-containing protein 2 (ATAD2), suggesting a potential therapeutic target for osteosarcoma treatment.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation and invasion
	Cell apoptosis
In-vitro Model	HOS	Osteosarcoma	Homo sapiens	CVCL_0312
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	METTL14 can promote osteosarcoma cell apoptosis, inhibit cell viability, and have a tumor suppressor effect on osteosarcoma. METTL14 finally achieves apoptosis by activating Caspase-3 (CASP3).
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	143B	Osteosarcoma	Homo sapiens	CVCL_2270
	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	YTHDF1 could recognize the m6A sites of CCR4-NOT transcription complex subunit 7 (CNOT7) and promote its expression in an m6A manner. Inhibition of YTHDF1 could suppress the proliferation, migration and invasion of the OS cells.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	HOS	Osteosarcoma	Homo sapiens	CVCL_0312
	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
In-vivo Model	The mice were divided into two groups with three mice in each group and their flank was subcutaneously injected with 1 × 107 OS cells. 28 days following subcutaneous injection, the mice were sacrificed through carbon dioxide euthanasia (30%/min) to obtain tumor weight and volume measurements.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	FTO could reduce the mRNA stability of Dapper homolog 1 (DACT1) via m6A demethylation, which decreased DACT1 expression and further activated the Wnt signaling pathway. The oncogenic effect of FTO on osteosarcoma was dependent on DACT1.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	ELAVL1 knockdown impaired the stability of DRG1 mRNA, thereby reducing both the mRNA and protein levels of Developmentally-regulated GTP-binding protein 1 (DRG1). In all, DRG1 exerted tumorigenic effects in osteosarcoma, and the up-regulation of DRG1 in OS was induced by METTL3 and ELAVL1 in an m6A-dependent manner.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell cycle
	Cell apoptosis
In-vitro Model	143B	Osteosarcoma	Homo sapiens	CVCL_2270
	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	ELAVL1 knockdown impaired the stability of DRG1 mRNA, thereby reducing both the mRNA and protein levels of Developmentally-regulated GTP-binding protein 1 (DRG1). In all, DRG1 exerted tumorigenic effects in osteosarcoma, and the up-regulation of DRG1 in OS was induced by METTL3 and ELAVL1 in an m6A-dependent manner.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	ELAV-like protein 1 (ELAVL1)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell cycle
	Cell apoptosis
In-vitro Model	143B	Osteosarcoma	Homo sapiens	CVCL_2270
	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[6]
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).
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
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.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	E3 ubiquitin-protein ligase TRIM7 (TRIM7) mRNA stability was regulated by the METTL3/14-YTHDF2-mRNA in a decay-dependent manner. TRIM7 plays a key role in regulating metastasis and chemoresistance in osteosarcoma through ubiquitination of BRMS1.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down 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
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	HOS	Osteosarcoma	Homo sapiens	CVCL_0312
	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
In-vivo Model	MG63 cells transduced with lentivirus expressing shTRIM7 or shNC, and SAOS2 cells transduced with lentivirus expressing TRIM7, BRMS1, TRIM7 plus BRMS1 or control vector, were injected via the tail vein into the nude mice (1 × 106 cells/mouse) (n = 11 per group).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	E3 ubiquitin-protein ligase TRIM7 (TRIM7) mRNA stability was regulated by the METTL3/14-YTHDF2-mRNA in a decay-dependent manner. TRIM7 plays a key role in regulating metastasis and chemoresistance in osteosarcoma through ubiquitination of BRMS1.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down 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
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	HOS	Osteosarcoma	Homo sapiens	CVCL_0312
	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
In-vivo Model	MG63 cells transduced with lentivirus expressing shTRIM7 or shNC, and SAOS2 cells transduced with lentivirus expressing TRIM7, BRMS1, TRIM7 plus BRMS1 or control vector, were injected via the tail vein into the nude mice (1 × 106 cells/mouse) (n = 11 per group).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	METTL3-mediated circNRIP1 exhibits oncogenic roles in osteosarcoma by regulating Forkhead box protein C2 (FOXC2) via sponging miR-199a, which provides new ideas for the treatment of osteosarcoma.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[9]
Response Summary	A remarkable m6A-modified site was found on the 3'-UTR of FOXD2-AS1, and m6A methyltransferase WTAP promoted the methylation modification, thus enhancing the stability of FOXD2-AS1 transcripts. m6A-modified FOXD2-AS1 accelerates the osteosarcoma progression through m6A manner, which provides new concepts for osteosarcoma tumorigenesis. FOXD2-AS1 interacted with downstream target FOXM1 mRNA through m6A sites, forming a FOXD2-AS1/m6A/Forkhead box protein M1 (FOXM1) complex to heighten FOXM1 mRNA stability.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	Wilms tumor 1-associating protein (WTAP)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
In-vivo Model	In vivo animal assay, FOXD2-AS1 overexpression promoted the tumor growth in mice subcutaneous injection

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[10]
Response Summary	Higher METTL3 expression indicated poorer prognosis. METTL3 upregulated Histone deacetylase 5 (HDAC5) expression in osteosarcoma cells by increasing the m6A level.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	HOS	Osteosarcoma	Homo sapiens	CVCL_0312
	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
In-vivo Model	U2OS cells with stable METTL3 expression were screened using puromycin for subsequent experiments. U2OS cells (1 × 106) were injected subcutaneously to the right side of each mouse (the mice were numbered according to their weight, and the experimenters randomly divided the nude mice into 12 groups by the random number method, with 12 mice in each group). The status of mice was detected every 2 days. Tumor growth and volume were measured once a week.Tumor volume was measured: Volume = Width2 × Length/2. On the 35th day after the operation, nude mice were euthanized by intraperitoneal injection of ≥100 mg/kg pentobarbital sodium. Tumor resection was performed and tumor weight was recorded. Weight loss >10% of the body weight or the maximum diameter of the tumor >1.5 cm was the humane end point.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[11]
Response Summary	Homeobox-containing protein 1 (HMBOX1) was identified as the target gene of WTAP, WTAP/HMBOX1 regulated osteosarcoma growth and metastasis via PI3K/AKT pathway.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	Wilms tumor 1-associating protein (WTAP)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
	SJSA-1	Osteosarcoma	Homo sapiens	CVCL_1697
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	HOS	Osteosarcoma	Homo sapiens	CVCL_0312
	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
	143B	Osteosarcoma	Homo sapiens	CVCL_2270
In-vivo Model	Nude mice (4 weeks, male) were used for tumor model.For the subcutaneous tumor model, 1 × 106 shNC, shWTAP or shHMBOX1 or shWTAP/shHMBOX1 U2OS cells seeded into mice via subcutaneous injection. Tumor volume and tumor weight were measured to analyze tumor growth as previous described. For orthotopic xenograft tumor model, shNC, shWTAP, shHMBOX1, or shWTAP/shHMBOX1 U2OS cells were labeled with a luminescent dye and GFP, and injected into the cavity of the tibia of mice. Thirty days after injection, tumor growth was detected. For the metastasis model, the cells were injected into the tail vein, and the lung metastasis were detected 30 days after injection using in vivo bioluminescence imaging system.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	METTL3 silence decreased the m6A methylation and total mRNA level of Lymphoid enhancer-binding factor 1 (LEF1),the m6A methyltransferase METTL3 promotes osteosarcoma cell progression by regulating the m6A level of LEF1 and activating Wnt/beta-catenin signaling pathway.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	HOS	Osteosarcoma	Homo sapiens	CVCL_0312
	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	The Metastatic Bone Tumor Model was established via injecting HOS cells into the right tibia of each animal.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[13]
Response Summary	METTL3 contributes to OS progression by increasing Putative uncharacterized protein DANCR (DANCR) mRNA stability via m6A modification, meaning that METTL3 is a promising therapeutic target for OS treatment.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
	SJSA-1	Osteosarcoma	Homo sapiens	CVCL_1697
	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	HOS	Osteosarcoma	Homo sapiens	CVCL_0312
	hFOB 1.19	Normal	Homo sapiens	CVCL_3708

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[14]
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.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
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
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[14]
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.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
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

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[14]
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.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
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
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[14]
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.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
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

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[15]
Response Summary	METTL3 is highly expressed in OS and enhances TNF receptor-associated factor 6 (TRAF6) expression through m6A modification, thereby promoting the metastases of OS cells.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	NHOst (Normal human osteoblast cells)
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	HOS	Osteosarcoma	Homo sapiens	CVCL_0312
In-vivo Model	For mouse xenograft tumor model, 1×106 Saos2 or HOS cells were mixed in 200 ul PBS and injected subcutaneously into 6- to 8-week-old C57BL/6 mice.umor size of mice was measured by vernier calipers every week after injection. The mice were euthanized after 28 days by intraperitoneal injection of 1% pentobarbital sodium (120 mg/kg), and the tumor tissues were removed from the mice.

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[16]
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.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
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.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[16]
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.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
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.
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[16]
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.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up 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.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[6]
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.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
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.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[17]
Response Summary	higher IGFBP-3 levels in osteosarcoma tissue compared with normal healthy tissue. IGFBP-3 treatment of two human osteosarcoma cell lines promoted cell migration and upregulated levels of Vascular cell adhesion protein 1 (VCAM1) expression via PI3K/Akt and AP-1 signaling.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	Insulin-like growth factor-binding protein 3 (IGFBP3)		READER	Regulator Info
Pathway Response	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[9]
Response Summary	A remarkable m6A-modified site was found on the 3'-UTR of FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1), and m6A methyltransferase WTAP promoted the methylation modification, thus enhancing the stability of FOXD2-AS1 transcripts. m6A-modified FOXD2-AS1 accelerates the osteosarcoma progression through m6A manner, which provides new concepts for osteosarcoma tumorigenesis. FOXD2-AS1 interacted with downstream target FOXM1 mRNA through m6A sites, forming a FOXD2-AS1/m6A/FOXM1 complex to heighten FOXM1 mRNA stability.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	Wilms tumor 1-associating protein (WTAP)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
In-vivo Model	In vivo animal assay, FOXD2-AS1 overexpression promoted the tumor growth in mice subcutaneous injection

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[18]
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.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
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.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[18]
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.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
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.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[16]
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.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
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.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[16]
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.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
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.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	METTL3-mediated circNRIP1 exhibits oncogenic roles in osteosarcoma by regulating FOXC2 via sponging hsa-miR-199a-5p, which provides new ideas for the treatment of osteosarcoma.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	METTL3-mediated hsa_circ_0004771 (circNRIP1) exhibits oncogenic roles in osteosarcoma by regulating FOXC2 via sponging miR-199a, which provides new ideas for the treatment of osteosarcoma.
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042

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Ref 2	METTL14 Overexpression Promotes Osteosarcoma Cell Apoptosis and Slows Tumor Progression via Caspase 3 Activation. Cancer Manag Res. 2020 Dec 11;12:12759-12767. doi: 10.2147/CMAR.S284273. eCollection 2020.
Ref 3	Methylation recognition protein YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) regulates the proliferation, migration and invasion of osteosarcoma by regulating m6A level of CCR4-NOT transcription complex subunit 7 (CNOT7). Bioengineered. 2022 Mar;13(3):5236-5250. doi: 10.1080/21655979.2022.2037381.
Ref 4	M(6)A demethylase FTO-mediated downregulation of DACT1 mRNA stability promotes Wnt signaling to facilitate osteosarcoma progression. Oncogene. 2022 Mar;41(12):1727-1741. doi: 10.1038/s41388-022-02214-z. Epub 2022 Feb 4.
Ref 5	m6A-dependent up-regulation of DRG1 by METTL3 and ELAVL1 promotes growth, migration, and colony formation in osteosarcoma. Biosci Rep. 2020 Apr 30;40(4):BSR20200282. doi: 10.1042/BSR20200282.
Ref 6	M6A RNA Methylation Regulates Histone Ubiquitination to Support Cancer Growth and Progression. Cancer Res. 2022 May 16;82(10):1872-1889. doi: 10.1158/0008-5472.CAN-21-2106.
Ref 7	N6-Methyladenosine modification of the TRIM7 positively regulates tumorigenesis and chemoresistance in osteosarcoma through ubiquitination of BRMS1. EBioMedicine. 2020 Sep;59:102955. doi: 10.1016/j.ebiom.2020.102955. Epub 2020 Aug 24.
Ref 8	Circular RNA circNRIP1 plays oncogenic roles in the progression of osteosarcoma. Mamm Genome. 2021 Dec;32(6):448-456. doi: 10.1007/s00335-021-09891-3. Epub 2021 Jul 10.
Ref 9	N(6)-methyladenosine methyltransferase WTAP-stabilized FOXD2-AS1 promotes the osteosarcoma progression through m(6)A/FOXM1 axis. Bioengineered. 2022 Apr;13(4):7963-7973. doi: 10.1080/21655979.2021.2008218.
Ref 10	METTL3 stabilizes HDAC5 mRNA in an m(6)A-dependent manner to facilitate malignant proliferation of osteosarcoma cells. Cell Death Discov. 2022 Apr 8;8(1):179. doi: 10.1038/s41420-022-00926-5.
Ref 11	WTAP promotes osteosarcoma tumorigenesis by repressing HMBOX1 expression in an m(6)A-dependent manner. Cell Death Dis. 2020 Aug 19;11(8):659. doi: 10.1038/s41419-020-02847-6.
Ref 12	The m6A methyltransferase METTL3 promotes osteosarcoma progression by regulating the m6A level of LEF1. Biochem Biophys Res Commun. 2019 Aug 27;516(3):719-725. doi: 10.1016/j.bbrc.2019.06.128. Epub 2019 Jun 26.
Ref 13	METTL3 Contributes to Osteosarcoma Progression by Increasing DANCR mRNA Stability via m6A Modification. Front Cell Dev Biol. 2022 Jan 12;9:784719. doi: 10.3389/fcell.2021.784719. eCollection 2021.
Ref 14	ALKBH5 regulates STAT3 activity to affect the proliferation and tumorigenicity of osteosarcoma via an m6A-YTHDF2-dependent manner. EBioMedicine. 2022 Jun;80:104019. doi: 10.1016/j.ebiom.2022.104019. Epub 2022 Apr 28.
Ref 15	m6A-dependent upregulation of TRAF6 by METTL3 is associated with metastatic osteosarcoma. J Bone Oncol. 2022 Jan 19;32:100411. doi: 10.1016/j.jbo.2022.100411. eCollection 2022 Feb.
Ref 16	ALKBH5 suppresses tumor progression via an m(6)A-dependent epigenetic silencing of pre-miR-181b-1/YAP signaling axis in osteosarcoma. Cell Death Dis. 2021 Jan 11;12(1):60. doi: 10.1038/s41419-020-03315-x.
Ref 17	IGFBP-3 stimulates human osteosarcoma cell migration by upregulating VCAM-1 expression. Life Sci. 2021 Jan 15;265:118758. doi: 10.1016/j.lfs.2020.118758. Epub 2020 Nov 12.
Ref 18	ALKBH5-mediated m(6)A demethylation of lncRNA PVT1 plays an oncogenic role in osteosarcoma. Cancer Cell Int. 2020 Jan 30;20:34. doi: 10.1186/s12935-020-1105-6. eCollection 2020.