Name	Prostate cancer
ICD	ICD-11: 2C82

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	ELF3 is a member of the ETS family of transcription factors, is a repressor of Androgen receptor (AR) transcriptional activity. Modulation of ELF3 expression and/or AR/ELF3 interaction has utility in the treatment of PC.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	ETS-related transcription factor Elf-3 (ELF3)		WRITER	Regulator Info
In-vitro Model	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	NOD.CB17-Prkdcscid/J none castrated SCID male mice 4 weeks old were purchased from Jackson Laboratories. After a one week period of acclimation, the mice were injected with 6×106 TetOn-Flag-ELF3 LNCaP suspended in 200 uL of a 50% mixture containing RPMI 1640 medium and Matrigel matrix basement membrane (BD Corporation, Bedford, MA) subcutaneously into the right flank region. The mice were either fed with doxycycline 200 mg/kg containing diet (BioServ, NJ) to induce the ELF3 expression or with a control regular diet. The sizes of the resultant tumors were measured weekly.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	FTO suppresses PCa proliferation and metastasis through reducing the degradation of Chloride intracellular channel protein 4 (CLIC4) mRNA in an m6A dependent manner.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	RWPE-1	Normal	Homo sapiens	CVCL_3791
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	LNCaP C4-2	Prostate carcinoma	Homo sapiens	CVCL_4782
In-vivo Model	Approximately 2×106 PCa cells (DU145 transfected with shFTO and shNC) were injected subcutaneously in mice. The tumor volume (V = (0.5*length*width2)) was measured with Vernier caliper every week. Ten mice were randomly divided into two groups, 2×106 cells transfected with shFTO and shNC were resuspended with 100 uL PBS and injected into the mouse tail vein to create a metastatic model. After 7 weeks, the mice were anesthetized, and D-luciferin (#D-Luciferin, Apexbio) was injected intraperitoneally, then used the IVIS imaging system (Caliper Life Sciences) to visualize the luciferase signal.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	m6A modification levels were markedly upregulated in human PCa tissues due to increased expression of METTL3. METTL3 mediates m6A modification of USP4 mRNA at A2696, and m6A reader protein YTHDF2 binds to and induces degradation of USP4 mRNA by recruiting RNA-binding protein HNRNPD to the mRNA. Decrease of USP4 fails to remove the ubiquitin group from ELAVL1 protein, resulting in a reduction of ELAVL1 protein. Lastly, downregulation of ELAV-like protein 1 (HuR/ELAVL1) in turn increases ARHGDIA expression, promoting migration and invasion of PCa cells.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
In-vivo Model	A total of 1 × 106 PC3 cells or DU145 cells suspended in a mixture of 100 uL PBS and Matrigel were subcutaneously injected into BALB/c nude mice. Tumor weight were measured 2 months after the engraftment. To evaluate the role of METTL3 in tumor metastasis, PC3 cells with or without knockdown of METTL3 were injected into SCID mice through the tail vein (1 × 106 cells per mouse). After eight weeks, mice were sacrificed and their lung tissues were collected for subsequent analyses.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	m6A modification levels were markedly upregulated in human PCa tissues due to increased expression of METTL3. METTL3 mediates m6A modification of USP4 mRNA at A2696, and m6A reader protein YTHDF2 binds to and induces degradation of USP4 mRNA by recruiting RNA-binding protein HNRNPD to the mRNA. Decrease of USP4 fails to remove the ubiquitin group from ELAV-like protein 1 (HuR/ELAVL1) protein, resulting in a reduction of ELAVL1 protein. Lastly, downregulation of ELAVL1 in turn increases ARHGDIA expression, promoting migration and invasion of PCa cells.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
In-vivo Model	A total of 1 × 106 PC3 cells or DU145 cells suspended in a mixture of 100 uL PBS and Matrigel were subcutaneously injected into BALB/c nude mice. Tumor weight were measured 2 months after the engraftment. To evaluate the role of METTL3 in tumor metastasis, PC3 cells with or without knockdown of METTL3 were injected into SCID mice through the tail vein (1 × 106 cells per mouse). After eight weeks, mice were sacrificed and their lung tissues were collected for subsequent analyses.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	Knock-down of YTHDF2 or METTL3 significantly induced the expression of LHPP and Homeobox protein Nkx-3.1 (NKX3-1) at both mRNA and protein level with inhibited phosphorylated AKT. YTHDF2 mediates the mRNA degradation of the tumor suppressors LHPP and NKX3-1 in m6A-dependent way to regulate AKT phosphorylation-induced tumor progression in prostate cancer.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Oxidative phosphorylation			hsa00190
In-vitro Model	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235
	RWPE-1	Normal	Homo sapiens	CVCL_3791
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	22Rv1	Prostate carcinoma	Homo sapiens	CVCL_1045
In-vivo Model	Approximately 2 × 106 PCa cells (PC-3 shNC, shYTHDF2, shMETTL3 cell lines) per mouse suspended in 100 uL PBS were injected in the flank of male BALB/c nude mice (4 weeks old). During the 40-day observation, the tumor size (V = (width2×length ×0.52)) was measured with vernier caliper. Approximately 1.5 × 106 PCa cells suspended in 100 uL of PBS (PC-3 shNC, shYTHDF2, and shMETTL3 cell lines) per mouse were injected into the tail vein of male BALB/c nude mice (4 weeks old). The IVIS Spectrum animal imaging system (PerkinElmer) was used to evaluate the tumor growth (40 days) and whole metastasis conditions (4 weeks and 6 weeks) with 100 uL XenoLight D-luciferin Potassium Salt (15 mg/ml, Perkin Elmer) per mouse. Mice were anesthetized and then sacrificed for tumors and metastases which were sent for further organ-localized imaging as above, IHC staining and hematoxylin-eosin (H&E) staining.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	Knock-down of YTHDF2 or METTL3 significantly induced the expression of LHPP and Homeobox protein Nkx-3.1 (NKX3-1) at both mRNA and protein level with inhibited phosphorylated AKT. YTHDF2 mediates the mRNA degradation of the tumor suppressors LHPP and NKX3-1 in m6A-dependent way to regulate AKT phosphorylation-induced tumor progression in prostate cancer.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Oxidative phosphorylation			hsa00190
In-vitro Model	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235
	RWPE-1	Normal	Homo sapiens	CVCL_3791
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	22Rv1	Prostate carcinoma	Homo sapiens	CVCL_1045
In-vivo Model	Approximately 2 × 106 PCa cells (PC-3 shNC, shYTHDF2, shMETTL3 cell lines) per mouse suspended in 100 uL PBS were injected in the flank of male BALB/c nude mice (4 weeks old). During the 40-day observation, the tumor size (V = (width2×length ×0.52)) was measured with vernier caliper. Approximately 1.5 × 106 PCa cells suspended in 100 uL of PBS (PC-3 shNC, shYTHDF2, and shMETTL3 cell lines) per mouse were injected into the tail vein of male BALB/c nude mice (4 weeks old). The IVIS Spectrum animal imaging system (PerkinElmer) was used to evaluate the tumor growth (40 days) and whole metastasis conditions (4 weeks and 6 weeks) with 100 uL XenoLight D-luciferin Potassium Salt (15 mg/ml, Perkin Elmer) per mouse. Mice were anesthetized and then sacrificed for tumors and metastases which were sent for further organ-localized imaging as above, IHC staining and hematoxylin-eosin (H&E) staining.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	METTL3-mediated m6A modification contributed to PCAT6 upregulation in an IGF2BP2-dependent manner. Furthermore, PCAT6 upregulated Insulin-like growth factor 1 receptor (IGF1R) expression by enhancing IGF1R mRNA stability through the PCAT6/IGF2BP2/IGF1R RNA-protein three-dimensional complex. The m6 A-induced PCAT6/IGF2BP2/IGF1R axis promotes PCa bone metastasis and tumor growth, suggesting that PCAT6 serves as a promising prognostic marker and therapeutic target against bone-metastatic PCa.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	RNA stability
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	LNCaP C4-2B	Prostate carcinoma	Homo sapiens	CVCL_4784
In-vivo Model	At 1 week post-injection with PC-3 cells, mice were randomly assigned to three groups (n = 8 per group): the ASO-NC group (injection with ASO negative control targeting unknown sequence, 5 nmol in 100 uL PBS for each mouse), the ASO-L group (injection with low-dose ASO targeting PCAT6, 5 nmol in 100 uL PBS for each mouse), and the ASO-H group (injection with high-dose ASO targeting PCAT6, 10 nmol in 100 uL PBS for each mouse).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	METTL3-mediated m6A modification contributed to PCAT6 upregulation in an IGF2BP2-dependent manner. Furthermore, PCAT6 upregulated Insulin-like growth factor 1 receptor (IGF1R) expression by enhancing IGF1R mRNA stability through the PCAT6/IGF2BP2/IGF1R RNA-protein three-dimensional complex. The m6 A-induced PCAT6/IGF2BP2/IGF1R axis promotes PCa bone metastasis and tumor growth, suggesting that PCAT6 serves as a promising prognostic marker and therapeutic target against bone-metastatic PCa.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	RNA stability
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	LNCaP C4-2B	Prostate carcinoma	Homo sapiens	CVCL_4784
In-vivo Model	At 1 week post-injection with PC-3 cells, mice were randomly assigned to three groups (n = 8 per group): the ASO-NC group (injection with ASO negative control targeting unknown sequence, 5 nmol in 100 uL PBS for each mouse), the ASO-L group (injection with low-dose ASO targeting PCAT6, 5 nmol in 100 uL PBS for each mouse), and the ASO-H group (injection with high-dose ASO targeting PCAT6, 10 nmol in 100 uL PBS for each mouse).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	METTL3 regulates the expression of Integrin beta-1 (ITGB1) through m6A-HuR-dependent mechanism, which affects the binding of ITGB1 to Collagen I and tumor cell motility, so as to promote the bone metastasis of prostate cancer.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Cell adhesion molecules			hsa04514
Cell Process	Cell adhesion
In-vitro Model	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
In-vivo Model	All the mice were randomly divided into five groups of four mice each, including PC3-shNC, PC3-shMETTL3-1/2, LNCaP-vector and LNCaP-METTL3 group.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	METTL3 induced m6A modification on Kinesin-like protein KIF3C (KIF3C), promoting the stabilization of KIF3C-mRNA by IGF2BP1. KIF3C was overexpressed in prostate cancer, promoting its growth migration and invasion was induced by miR-320d/METTL3 in an m6A dependent process.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell migration
	Cell invasion
In-vitro Model	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	LNCaP C4-2B	Prostate carcinoma	Homo sapiens	CVCL_4784
	22Rv1	Prostate carcinoma	Homo sapiens	CVCL_1045
In-vivo Model	For the proliferation assays, C4-2B cells of KIF3C knockdown, negative control (1×106/200uL) were subcutaneously injected into BALB/c nude mice. The tumors were dissected and weighed (4-6 weeks old, male).

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 influences the activity of the Wnt pathway through m6A methylation on Lymphoid enhancer-binding factor 1 (LEF1) mRNA, thereafter, promoting the progression of prostate cancer.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Cell activity and migratory
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[9]
Response Summary	FTO was downregulated in PCa and its expression level showed a relevance to the prognosis of PCa patients. Additionally, FTO could regulate the proliferation, migration and invasion of PCa via regulating the expression level of Melanocortin receptor 4 (MC4R).
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Down regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	WPMY-1	Normal	Homo sapiens	CVCL_3814
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	22Rv1	Prostate carcinoma	Homo sapiens	CVCL_1045
In-vivo Model	PCa cells carrying the transfected plasmid were subcutaneously injected into immunodeficient mice at a rate of 1 × 106 cells per mouse according to a previous study. Tumor formation in the two groups of mice was observed and recorded by a designated personnel every day, and the volume of the tumors was measured. The nude mice were sacrificed 21 days after tumor formation, and the tumors were removed to measure their volume and weight.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[10]
Response Summary	METTL3 promoted cell proliferation, migration, invasion and tumorigenesis in PCa. METTL3 upregulating the level of m6A, and interacted with Microprocessor complex subunit DGCR8 (DGCR8) to recognize the m6A modification of pre-miR-182 to regulate its splicing and maturation and promote the high expression of miRNA.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	UP regulation
In-vitro Model	WPMY-1	Normal	Homo sapiens	CVCL_3814
	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[11]
Response Summary	Activation of the KDM5A/miRNA-495/YTHDF2/m6A-MOB3B axis facilitates prostate cancer progression. YTHDF2 could inhibit MOB kinase activator 3B (MOB3B) expression by recognizing m6A modification of MOB3B mRNA and inducing mRNA degradation.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	LNCaP C4-2	Prostate carcinoma	Homo sapiens	CVCL_4782
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
In-vivo Model	Under anesthesia with ether, the nude mice were disinfected and subcutaneously inoculated with cells transfected with oe-NC, oe-KDM5A + oe-NC and oe-KDM5A + oe-MOB3B at a density of 1 × 106 cells/mouse (200 uL) at the back of the right hind leg.

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 enhanced Myc proto-oncogene protein (MYC) expression by increasing m6A levels of MYC mRNA transcript, leading to oncogenic functions in prostate cancer.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	LNCaP C4-2	Prostate carcinoma	Homo sapiens	CVCL_4782
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	Knock-down of YTHDF2 or METTL3 significantly induced the expression of Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) and NKX3-1 at both mRNA and protein level with inhibited phosphorylated AKT. YTHDF2 mediates the mRNA degradation of the tumor suppressors LHPP and NKX3-1 in m6A-dependent way to regulate AKT phosphorylation-induced tumor progression in prostate cancer.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Oxidative phosphorylation			hsa00190
In-vitro Model	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235
	RWPE-1	Normal	Homo sapiens	CVCL_3791
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	22Rv1	Prostate carcinoma	Homo sapiens	CVCL_1045
In-vivo Model	Approximately 2 × 106 PCa cells (PC-3 shNC, shYTHDF2, shMETTL3 cell lines) per mouse suspended in 100 uL PBS were injected in the flank of male BALB/c nude mice (4 weeks old). During the 40-day observation, the tumor size (V = (width2×length ×0.52)) was measured with vernier caliper. Approximately 1.5 × 106 PCa cells suspended in 100 uL of PBS (PC-3 shNC, shYTHDF2, and shMETTL3 cell lines) per mouse were injected into the tail vein of male BALB/c nude mice (4 weeks old). The IVIS Spectrum animal imaging system (PerkinElmer) was used to evaluate the tumor growth (40 days) and whole metastasis conditions (4 weeks and 6 weeks) with 100 uL XenoLight D-luciferin Potassium Salt (15 mg/ml, Perkin Elmer) per mouse. Mice were anesthetized and then sacrificed for tumors and metastases which were sent for further organ-localized imaging as above, IHC staining and hematoxylin-eosin (H&E) staining.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	Knock-down of YTHDF2 or METTL3 significantly induced the expression of Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) and NKX3-1 at both mRNA and protein level with inhibited phosphorylated AKT. YTHDF2 mediates the mRNA degradation of the tumor suppressors LHPP and NKX3-1 in m6A-dependent way to regulate AKT phosphorylation-induced tumor progression in prostate cancer.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Oxidative phosphorylation			hsa00190
In-vitro Model	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235
	RWPE-1	Normal	Homo sapiens	CVCL_3791
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	22Rv1	Prostate carcinoma	Homo sapiens	CVCL_1045
In-vivo Model	Approximately 2 × 106 PCa cells (PC-3 shNC, shYTHDF2, shMETTL3 cell lines) per mouse suspended in 100 uL PBS were injected in the flank of male BALB/c nude mice (4 weeks old). During the 40-day observation, the tumor size (V = (width2×length ×0.52)) was measured with vernier caliper. Approximately 1.5 × 106 PCa cells suspended in 100 uL of PBS (PC-3 shNC, shYTHDF2, and shMETTL3 cell lines) per mouse were injected into the tail vein of male BALB/c nude mice (4 weeks old). The IVIS Spectrum animal imaging system (PerkinElmer) was used to evaluate the tumor growth (40 days) and whole metastasis conditions (4 weeks and 6 weeks) with 100 uL XenoLight D-luciferin Potassium Salt (15 mg/ml, Perkin Elmer) per mouse. Mice were anesthetized and then sacrificed for tumors and metastases which were sent for further organ-localized imaging as above, IHC staining and hematoxylin-eosin (H&E) staining.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	Knock-down of YTHDF2 or METTL3 significantly induced the expression of LHPP and NKX3-1 at both mRNA and protein level with inhibited phosphorylated RAC-alpha serine/threonine-protein kinase (AKT1). YTHDF2 mediates the mRNA degradation of the tumor suppressors LHPP and NKX3-1 in m6A-dependent way to regulate AKT phosphorylation-induced tumor progression in prostate cancer.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Oxidative phosphorylation			hsa00190
In-vitro Model	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235
	RWPE-1	Normal	Homo sapiens	CVCL_3791
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	22Rv1	Prostate carcinoma	Homo sapiens	CVCL_1045
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	Knock-down of YTHDF2 or METTL3 significantly induced the expression of LHPP and NKX3-1 at both mRNA and protein level with inhibited phosphorylated RAC-alpha serine/threonine-protein kinase (AKT1). YTHDF2 mediates the mRNA degradation of the tumor suppressors LHPP and NKX3-1 in m6A-dependent way to regulate AKT phosphorylation-induced tumor progression in prostate cancer.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Oxidative phosphorylation			hsa00190
In-vitro Model	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235
	RWPE-1	Normal	Homo sapiens	CVCL_3791
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	22Rv1	Prostate carcinoma	Homo sapiens	CVCL_1045
In-vivo Model	Approximately 2 × 106 PCa cells (PC-3 shNC, shYTHDF2, shMETTL3 cell lines) per mouse suspended in 100 uL PBS were injected in the flank of male BALB/c nude mice (4 weeks old). During the 40-day observation, the tumor size (V = (width2×length ×0.52)) was measured with vernier caliper. Approximately 1.5 × 106 PCa cells suspended in 100 uL of PBS (PC-3 shNC, shYTHDF2, and shMETTL3 cell lines) per mouse were injected into the tail vein of male BALB/c nude mice (4 weeks old). The IVIS Spectrum animal imaging system (PerkinElmer) was used to evaluate the tumor growth (40 days) and whole metastasis conditions (4 weeks and 6 weeks) with 100 uL XenoLight D-luciferin Potassium Salt (15 mg/ml, Perkin Elmer) per mouse. Mice were anesthetized and then sacrificed for tumors and metastases which were sent for further organ-localized imaging as above, IHC staining and hematoxylin-eosin (H&E) staining.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[13]
Response Summary	In prostate cancer, METTL14 downregulated Thrombospondin-1 (THBS1) expression in an m6A-dependent manner, which resulted in the recruitment of YTHDF2 to recognize and degrade Thrombospondin 1 (THBS1) mRNA.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	Cell proliferation
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
In-vivo Model	Stably transfected shMETTL14 and shNC DU145 cells (5×106 cells) suspended in a mixture of 100uL PBS were subcutaneously injected into the right flank of male nude BALB/C mice (6-8 weeks old) to induce tumor formation.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[13]
Response Summary	In prostate cancer, METTL14 downregulated Thrombospondin-1 (THBS1) expression in an m6A-dependent manner, which resulted in the recruitment of YTHDF2 to recognize and degrade Thrombospondin 1 (THBS1) mRNA.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	Cell proliferation
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
In-vivo Model	Stably transfected shMETTL14 and shNC DU145 cells (5×106 cells) suspended in a mixture of 100uL PBS were subcutaneously injected into the right flank of male nude BALB/C mice (6-8 weeks old) to induce tumor formation.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	m6A modification levels were markedly upregulated in human PCa tissues due to increased expression of METTL3. METTL3 mediates m6A modification of Ubiquitin carboxyl-terminal hydrolase 4 (USP4) mRNA at A2696, and m6A reader protein YTHDF2 binds to and induces degradation of USP4 mRNA by recruiting RNA-binding protein HNRNPD to the mRNA. Decrease of USP4 fails to remove the ubiquitin group from ELAVL1 protein, resulting in a reduction of ELAVL1 protein. Lastly, downregulation of ELAVL1 in turn increases ARHGDIA expression, promoting migration and invasion of PCa cells.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
In-vivo Model	A total of 1 × 106 PC3 cells or DU145 cells suspended in a mixture of 100 uL PBS and Matrigel were subcutaneously injected into BALB/c nude mice. Tumor weight were measured 2 months after the engraftment. To evaluate the role of METTL3 in tumor metastasis, PC3 cells with or without knockdown of METTL3 were injected into SCID mice through the tail vein (1 × 106 cells per mouse). After eight weeks, mice were sacrificed and their lung tissues were collected for subsequent analyses.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	m6A modification levels were markedly upregulated in human PCa tissues due to increased expression of METTL3. METTL3 mediates m6A modification of Ubiquitin carboxyl-terminal hydrolase 4 (USP4) mRNA at A2696, and m6A reader protein YTHDF2 binds to and induces degradation of USP4 mRNA by recruiting RNA-binding protein HNRNPD to the mRNA. Decrease of USP4 fails to remove the ubiquitin group from ELAVL1 protein, resulting in a reduction of ELAVL1 protein. Lastly, downregulation of ELAVL1 in turn increases ARHGDIA expression, promoting migration and invasion of PCa cells.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
In-vivo Model	A total of 1 × 106 PC3 cells or DU145 cells suspended in a mixture of 100 uL PBS and Matrigel were subcutaneously injected into BALB/c nude mice. Tumor weight were measured 2 months after the engraftment. To evaluate the role of METTL3 in tumor metastasis, PC3 cells with or without knockdown of METTL3 were injected into SCID mice through the tail vein (1 × 106 cells per mouse). After eight weeks, mice were sacrificed and their lung tissues were collected for subsequent analyses.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[14]
Response Summary	METTL3 silence decreased the m6A modification and expression of Zinc finger protein GLI1 (GLI1), an important component of hedgehog pathway, which led to cell apoptosis.the m6A methyltransferase METTL3 promotes the growth and motility of prostate cancer cells by regulating hedgehog pathway.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Hedgehog signaling pathway			hsa04340
Cell Process	Cell proliferation
	Cell survival
	Cell colony formation
	Cell invasion
In-vitro Model	LNCaP C4-2	Prostate carcinoma	Homo sapiens	CVCL_4782
	LNCaP C4-2B	Prostate carcinoma	Homo sapiens	CVCL_4784
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
In-vivo Model	Equal number of PC-3 cells was injected subcutaneously into right flank.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[15]
Response Summary	VIRMA downregulation attenuates the aggressive phenotype of prostate cancer by overall reduction of m6A-levels decreasing stability and abundance of oncogenic lncRNAs. VIRMA depletion and m6A reduction decreased the stability and abundance of Colon cancer associated transcript 1 (CCAT1) transcripts.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	RNA stability
In-vitro Model	22Rv1	Prostate carcinoma	Homo sapiens	CVCL_1045
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[15]
Response Summary	VIRMA downregulation attenuates the aggressive phenotype of prostate cancer by overall reduction of m6A-levels decreasing stability and abundance of oncogenic lncRNAs. VIRMA depletion and m6A reduction decreased the stability and abundance of Colon cancer associated transcript 2 (CCAT2) transcripts.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	RNA stability
In-vitro Model	22Rv1	Prostate carcinoma	Homo sapiens	CVCL_1045
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	METTL3-mediated m6A modification contributed to Prostate cancer associated transcript 6 (PCAT6) upregulation in an IGF2BP2-dependent manner. Furthermore, PCAT6 upregulated IGF1R expression by enhancing IGF1R mRNA stability through the PCAT6/IGF2BP2/IGF1R RNA-protein three-dimensional complex. The m6 A-induced PCAT6/IGF2BP2/IGF1R axis promotes PCa bone metastasis and tumor growth, suggesting that PCAT6 serves as a promising prognostic marker and therapeutic target against bone-metastatic PCa.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	RNA stability
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	LNCaP C4-2B	Prostate carcinoma	Homo sapiens	CVCL_4784
In-vivo Model	At 1 week post-injection with PC-3 cells, mice were randomly assigned to three groups (n = 8 per group): the ASO-NC group (injection with ASO negative control targeting unknown sequence, 5 nmol in 100 uL PBS for each mouse), the ASO-L group (injection with low-dose ASO targeting PCAT6, 5 nmol in 100 uL PBS for each mouse), and the ASO-H group (injection with high-dose ASO targeting PCAT6, 10 nmol in 100 uL PBS for each mouse).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	METTL3-mediated m6A modification contributed to Prostate cancer associated transcript 6 (PCAT6) upregulation in an IGF2BP2-dependent manner. Furthermore, PCAT6 upregulated IGF1R expression by enhancing IGF1R mRNA stability through the PCAT6/IGF2BP2/IGF1R RNA-protein three-dimensional complex. The m6 A-induced PCAT6/IGF2BP2/IGF1R axis promotes PCa bone metastasis and tumor growth, suggesting that PCAT6 serves as a promising prognostic marker and therapeutic target against bone-metastatic PCa.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	RNA stability
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	LNCaP C4-2B	Prostate carcinoma	Homo sapiens	CVCL_4784
In-vivo Model	At 1 week post-injection with PC-3 cells, mice were randomly assigned to three groups (n = 8 per group): the ASO-NC group (injection with ASO negative control targeting unknown sequence, 5 nmol in 100 uL PBS for each mouse), the ASO-L group (injection with low-dose ASO targeting PCAT6, 5 nmol in 100 uL PBS for each mouse), and the ASO-H group (injection with high-dose ASO targeting PCAT6, 10 nmol in 100 uL PBS for each mouse).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[16]
Response Summary	METTL3-stabilized lncRNA Small nucleolar RNA host gene (SNHG7) accelerates glycolysis in PCa via SRSF1/c-Myc axis and inspires the understanding of m6A roles in lncRNA metabolism and tumor progression.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Central carbon metabolism in cancer			hsa05230
	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glycolysis
In-vitro Model	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235
	RWPE-1	Normal	Homo sapiens	CVCL_3791
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[10]
Response Summary	METTL3 promoted cell proliferation, migration, invasion and tumorigenesis in PCa. METTL3 upregulating the level of m6A, and interacted with DGCR8 to recognize the m6A modification of pre-miR-182 to regulate its splicing and maturation and promote the high expression of miRNA.
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	UP regulation
In-vitro Model	WPMY-1	Normal	Homo sapiens	CVCL_3814
	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105

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Ref 11	Activation of the KDM5A/miRNA-495/YTHDF2/m6A-MOB3B axis facilitates prostate cancer progression. J Exp Clin Cancer Res. 2020 Oct 21;39(1):223. doi: 10.1186/s13046-020-01735-3.
Ref 12	The M6A methyltransferase METTL3 promotes the development and progression of prostate carcinoma via mediating MYC methylation. J Cancer. 2020 Mar 25;11(12):3588-3595. doi: 10.7150/jca.42338. eCollection 2020.
Ref 13	METTL14 promotes prostate tumorigenesis by inhibiting THBS1 via an m6A-YTHDF2-dependent mechanism. Cell Death Discov. 2022 Mar 30;8(1):143. doi: 10.1038/s41420-022-00939-0.
Ref 14	RNA m(6)A Methyltransferase METTL3 Promotes The Growth Of Prostate Cancer By Regulating Hedgehog Pathway. Onco Targets Ther. 2019 Nov 5;12:9143-9152. doi: 10.2147/OTT.S226796. eCollection 2019.
Ref 15	VIRMA-Dependent N6-Methyladenosine Modifications Regulate the Expression of Long Non-Coding RNAs CCAT1 and CCAT2 in Prostate Cancer. Cancers (Basel). 2020 Mar 25;12(4):771. doi: 10.3390/cancers12040771.
Ref 16	METTL3-stabilized lncRNA SNHG7 accelerates glycolysis in prostate cancer via SRSF1/c-Myc axis. Exp Cell Res. 2022 Jul 1;416(1):113149. doi: 10.1016/j.yexcr.2022.113149. Epub 2022 Apr 9.