Name	Colorectal cancer
ICD	ICD-11: 2B91

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	Knockdown of METTL14 significantly enhanced Arrestin domain-containing protein 4 (ARRDC4) mRNA stability relying on the "reader" protein YHTDF2 dependent manner in colorectal cancer.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015), RNA degradation
Cell Process	RNA stability
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	NCM460	Normal	Homo sapiens	CVCL_0460
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	HCT 15	Colon adenocarcinoma	Homo sapiens	CVCL_0292
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
In-vivo Model	Equal amount of HCT116 cells (2 × 106) stably expression of relevant plasmids was injected into the right flank of mice, tumor bulks was monitored once a week after injection and volumes were counted as 0.5 × a2 × b (a and b respectively indicated short and long diameter of tumor).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	Knockdown of METTL14 significantly enhanced Arrestin domain-containing protein 4 (ARRDC4) mRNA stability relying on the "reader" protein YTHDF2 dependent manner in colorectal cancer.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015), RNA degradation
Cell Process	RNA stability
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	NCM460	Normal	Homo sapiens	CVCL_0460
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	HCT 15	Colon adenocarcinoma	Homo sapiens	CVCL_0292
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
In-vivo Model	Equal amount of HCT116 cells (2 × 106) stably expression of relevant plasmids was injected into the right flank of mice, tumor bulks was monitored once a week after injection and volumes were counted as 0.5 × a2 × b (a and b respectively indicated short and long diameter of tumor).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	IGF2BP3, directly bound to the m6A-modified region of ATP-dependent translocase ABCB1 (ABCB1) mRNA, thereby promoting the stability and expression of ABCB1 mRNA. The expression of IGF2BP3 and ABCB1 was strongly correlated with DOX sensitivity. Targeting IGF2BP3 was an important chemotherapeutic strategy for preventing MDR development in colorectal cancer.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	ABC transporters			hsa02010
Cell Process	RNA stability
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 15	Colon adenocarcinoma	Homo sapiens	CVCL_0292
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	SW1463	Rectal adenocarcinoma	Homo sapiens	CVCL_1718
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	HCT8/T xenografts derived from shNC or shIGF2BP3-1 HCT8/T cells were established through subcutaneous inoculation of cells (6×106) into nude mice.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and C-X-C motif chemokine 10 (Cxcl10) in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 106 CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and C-X-C motif chemokine 10 (Cxcl10) in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 106 CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, C-X-C motif chemokine 9 (Cxcl9), and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 106 CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, C-X-C motif chemokine 9 (Cxcl9), and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 106 CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	Silencing YTHDF1 significantly inhibited Wnt/Catenin beta-1 (CTNNB1/Beta-catenin) pathway activity in Colorectal cancer cells.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
	Signaling pathways regulating pluripotency of stem cells			hsa04550
Cell Process	Cell Tumorigenicity
In-vitro Model	NCM460	Normal	Homo sapiens	CVCL_0460
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	1 × 105 parental HT29-shNC cells, HT29-shYTHDF1 cells, HT29-shNC colonospheres, and HT29-shYTHDF1 colonospheres were inoculated subcutaneously into the left inguinal folds of the nude mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	METTL3 promoted Class E basic helix-loop-helix protein 41 (BHLHE41) expression in m6A-dependent manner, which subsequently induced CXCL1 transcription to enhance MDSC migration in vitro. METTL3 as a potential therapeutic target for CRC immunotherapy whose inhibition reverses immune suppression through m6A-BHLHE41-CXCL1 axis.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Cytokine-cytokine receptor interaction			hsa04060
	Chemokine signaling pathway			hsa04062
Cell Process	Cell immunity
	Cell growth
	Cell migration
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	MC-38	Mouse colon adenocarcinoma	Mus musculus	CVCL_B288
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	METTL3 knockout or control CT26 and MC38 cells were injected subcutaneously into the dorsal flank of each 4- to 6-week-old male immunocompetent BALB/c and C57BL/6 mice, respectively. Anti-Gr-1 (BE0075; Bio-X-Cell, Lebanon, NH) or immunoglobulin (Ig)G isotype control (BE0090, Bio-XCell) was given every other day via intraperitoneal injection (150 ug/mouse). SB-265610 (Tocris, Bristol, UK) or phosphate-buffered saline was administrated through intraperitoneal injections at a dosage of 2 mg/kg per day. Tumor sizes were measured every other day. To establish an orthotopic mouse model of CRC, 5- to 6-week-old male C57BL/6 mice were treated with 1.7% dextran sodium sulfate in drinking water for 5 days, and then allowed to recover for 3 days. After 24 hours of fasting, METTL3 knockout or control MC38 cells suspended in 50 ul of 1 mg/mL Matrigel-phosphate-buffered saline (Corning, Corning, NY) were instilled into the colon lumen of anesthetized mice, coated sparingly with Vaseline.

In total 4 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Asparagine inhibitor		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Asparagine inhibitor		Approved	Drug Info
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Cyclic AMP-dependent transcription factor ATF-4 (ATF4) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Chloroquine		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Experiment 4 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Cyclic AMP-dependent transcription factor ATF-4 (ATF4) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Meclofenamate sodium		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	The RP11/hnRNPA2B1/mRNA complex accelerated the mRNA degradation of two E3 ligases, E3 ubiquitin-protein ligase SIAH1 (SIAH1) and Fbxo45, and subsequently prevented the proteasomal degradation of Zeb1. m6A can regulate the expression of RP11, further, RP11 regulated Siah1-Fbxo45/Zeb1 was involved in the development of Colorectal cancer.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Proteasome			hsa03050
Cell Process	Proteasomal degradation
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 15	Colon adenocarcinoma	Homo sapiens	CVCL_0292
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
In-vivo Model	HCT-15 RP11 stable overexpression or control cells (2 × 106 per mouse) diluted in 100 uL normal medium + 100 uL Matrigel (BD Biosciences) were subcutaneously injected into immunodeficient mice to investigate tumour growth.

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	Ephrin type-A receptor 2 (EphA2) and VEGFA targeted by METTL3 via different IGF2BP-dependent mechanisms were found to promote vasculogenic mimicry (VM) formation via PI3K/AKT/mTOR and ERK1/2 signaling in CRC.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Pathway Response	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	NCM460	Normal	Homo sapiens	CVCL_0460
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
In-vivo Model	A total of 8 × 106 wild-type (WT) or METTL3-knockdown cells were injected into the dorsal flanks of 6-week-old nude mice. Seven mice were randomly selected to calculate the volume according to the following formula: V = (width2 × length)/2. Mice were euthanized three weeks after injection and tumors removed, weighed, fixed, and embedded for immunohistochemical analysis.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	Ephrin type-A receptor 2 (EphA2) and VEGFA targeted by METTL3 via different IGF2BP3-dependent mechanisms were found to promote vasculogenic mimicry (VM) formation via PI3K/AKT/mTOR and ERK1/2 signaling in CRC.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	NCM460	Normal	Homo sapiens	CVCL_0460
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
In-vivo Model	A total of 8 × 106 wild-type (WT) or METTL3-knockdown cells were injected into the dorsal flanks of 6-week-old nude mice. Seven mice were randomly selected to calculate the volume according to the following formula: V = (width2 × length)/2. Mice were euthanized three weeks after injection and tumors removed, weighed, fixed, and embedded for immunohistochemical analysis.
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	Ephrin type-A receptor 2 (EphA2) and VEGFA targeted by METTL3 via different IGF2BP2-dependent mechanisms were found to promote vasculogenic mimicry (VM) formation via PI3K/AKT/mTOR and ERK1/2 signaling in CRC.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	NCM460	Normal	Homo sapiens	CVCL_0460
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
In-vivo Model	A total of 8 × 106 wild-type (WT) or METTL3-knockdown cells were injected into the dorsal flanks of 6-week-old nude mice. Seven mice were randomly selected to calculate the volume according to the following formula: V = (width2 × length)/2. Mice were euthanized three weeks after injection and tumors removed, weighed, fixed, and embedded for immunohistochemical analysis.

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 played a tumor-suppressive role in Colorectal cancer cell proliferation, migration and invasion through p38/Ephrin type-B receptor 2 (ERK/EPHB2) pathways, which indicated that METTL3 was a novel marker for CRC carcinogenesis, progression and survival.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	MAPK signaling pathway			hsa04010
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	KM12	Colon carcinoma	Homo sapiens	CVCL_1331

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[10]
Response Summary	WM_Score correlated highly with the regulation of transcription and post-transcriptional events contributing to the development of colorectal cancer. In response to anti-cancer drugs, WM_Score highly negatively correlated (drug sensitive) with drugs which targeted oncogenic related pathways, such as MAPK, Epidermal growth factor receptor (EGFR), and mTOR signaling pathways, positively correlated (drug resistance) with drugs which targeted in apoptosis and cell cycle. Importantly, the WM_Score was associated with the therapeutic efficacy of PD-L1 blockade, suggesting that the development of potential drugs targeting these "writers" to aid the clinical benefits of immunotherapy.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Pathway Response	MAPK signaling pathway			hsa04010
	VEGF signaling pathway			hsa04370
	mTOR signaling pathway			hsa04150
	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Cell apoptosis

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	The RP11/hnRNPA2B1/mRNA complex accelerated the mRNA degradation of two E3 ligases, Siah1 and F-box/SPRY domain-containing protein 1 (FBXO45), and subsequently prevented the proteasomal degradation of Zeb1. m6A can regulate the expression of RP11, further, RP11 regulated Siah1-Fbxo45/Zeb1 was involved in the development of Colorectal cancer.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Proteasome			hsa03050
Cell Process	Proteasomal degradation
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 15	Colon adenocarcinoma	Homo sapiens	CVCL_0292
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
In-vivo Model	HCT-15 RP11 stable overexpression or control cells (2 × 106 per mouse) diluted in 100 uL normal medium + 100 uL Matrigel (BD Biosciences) were subcutaneously injected into immunodeficient mice to investigate tumour growth.

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

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 promotes colorectal cancer proliferation by stabilizing G1/S-specific cyclin-E1 (CCNE1) mRNA in an m6A-dependent manner, representing a promising therapeutic strategy for the treatment of CRC.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell proliferation
	Arrest cell cycle at G1 phase
In-vitro Model	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
In-vivo Model	LoVo cells (5 × 106 cells/ 200 uL PBS) stably transfected with METTL3 knockdown lentiviral vector or control vector were respectively injected subcutaneously into the left flank of each mouse.

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[13]
Response Summary	METTL3 stabilizes HK2 and Glucose transporter type 1 (SLC2A1) (GLUT1) expression in colorectal cancer through an m6A-IGF2BP2/3- dependent mechanism.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glucose metabolism
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[13]
Response Summary	METTL3 stabilizes HK2 and Glucose transporter type 1 (SLC2A1) (GLUT1) expression in colorectal cancer through an m6A-IGF2BP2/3- dependent mechanism.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glucose metabolism
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[14]
Response Summary	METTL3 induced Glucose transporter type 1 (SLC2A1) translation in an m6A-dependent manner, which subsequently promoted glucose uptake and lactate production, leading to the activation of mTORC1 signaling and CRC development.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
In-vivo Model	To generate the Mettl3+/- mice, 2 specific single-guide RNAs (sgRNAs) targeting exon 2 of Mettl3 were used, which resulted in a frameshift mutation and generated a premature stop codon.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[15]
Response Summary	Targeting FTO significantly suppresses cancer cell growth and enhances chemotherapy sensitivity, which not only mediating the balance of intracellular ROS by regulating Glucose-6-phosphate dehydrogenase (G6PD) expression, but also maintaining genome instability by regulating PARP1 expression. These findings shed light on new molecular mechanisms of CRC development and treatments mediated by m6A modification.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Glutathione metabolism			hsa00480
In-vitro Model	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	For CDX model, nude mice (female, 4-6-week-old) were subcutaneously injected with 5 × 106 HCT116 cells on the both flank. For PDX model, the patient tumors were divided into small pieces and then inoculated on both flank of nude mice. For knockdown FTO mice model, FTO mice model, two weeks after inoculation, the shFTO#3 lenti-virus injected into the tumor for three consecutive days. For combined medication mice model, intraperitoneal injection of Rhein and Olaparib was started one week after inoculation

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[13]
Response Summary	METTL3 stabilizes Hexokinase-2 (HK2) and SLC2A1 (GLUT1) expression in colorectal cancer through an m6A-IGF2BP2/3- dependent mechanism.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glucose metabolism
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[13]
Response Summary	METTL3 stabilizes Hexokinase-2 (HK2) and SLC2A1 (GLUT1) expression in colorectal cancer through an m6A-IGF2BP2/3- dependent mechanism.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glucose metabolism
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[16]
Response Summary	KIAA1429 has the potential to promote CRC carcinogenesis by targeting Hexokinase-2 (HK2) via m6A-independent manner, providing insight into the critical roles of m6A in CRC.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	Metabolic pathways			hsa01100
	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glycolysis
In-vitro Model	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	FHC	Normal	Homo sapiens	CVCL_3688

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[17]
Response Summary	LINC00460 is a novel oncogene of colorectal cancer through interacting with IGF2BP2 and DHX9 and bind to the m6A modified High mobility group protein HMG-I/HMG-Y (HMGA1) mRNA to enhance the HMGA1 mRNA stability. The N6-methyladenosine (m6A) modification of HMGA1 mRNA by METTL3 enhanced HMGA1 expression in CRC.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Cell Process	mRNA stability
	Epithelial-mesenchymal transition
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	FHC	Normal	Homo sapiens	CVCL_3688
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	Groups of HCT116-Luc-shCtrl, HCT116-Luc-shLINC00460, and HCT116-Luc-shLINC00460 + HMGA1 cells (5 × 106) were injected subcutaneously into the flanks of mice correspondingly.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[17]
Response Summary	LINC00460 is a novel oncogene of colorectal cancer through interacting with IGF2BP2 and DHX9 and bind to the m6A modified High mobility group protein HMG-I/HMG-Y (HMGA1) mRNA to enhance the HMGA1 mRNA stability. The N6-methyladenosine (m6A) modification of HMGA1 mRNA by METTL3 enhanced HMGA1 expression in CRC.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Cell Process	mRNA stability
	Epithelial-mesenchymal transition
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	FHC	Normal	Homo sapiens	CVCL_3688
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	Groups of HCT116-Luc-shCtrl, HCT116-Luc-shLINC00460, and HCT116-Luc-shLINC00460 + HMGA1 cells (5 × 106) were injected subcutaneously into the flanks of mice correspondingly.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of Interferon gamma (IFN-gamma), Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 106 CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of Interferon gamma (IFN-gamma), Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 106 CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Interferon regulatory factor 1 (Irf1) mRNA via Ythdf2.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 106 CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Interferon regulatory factor 1 (Irf1) mRNA via Ythdf2.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 106 CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Interferon regulatory factor 1 (Irf1) mRNA via Ythdf2.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 106 CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[18]
Response Summary	The study highlights a robust correlation between the level of cancer stemness and traits related to tumor heterogeneity, including the immune microenvironment, TMB, and the expression of m6A RNA methylation regulatory factors in colorectal cancer cells. A three-gene prognostic signature (PARPBP, KNSTRN, and Kinesin-like protein KIF2C (KIF2C)) was explored together with specific clinical features to construct a nomogram, which was successfully validated in an external cohort.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[19]
Response Summary	The expression of METTL14 was downregulated in CRC cells and METTL14 could inhibit the metastasis of CRC cells. MeCP2 could bind to METTL14 to coregulate tumor suppressor Krueppel-like factor 4 (KLF4) expression through changing m6 A methylation modification.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
In-vivo Model	In vivo, the group of HCT116 cells labeled with luciferase were surgically injected into the spleen of nude mice. After 2 months, the nude mice were subjected to D-luciferin injection and the luciferase signals were monitored and quantified.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[20]
Response Summary	METTL3 enhances the expression of Lactate dehydrogenase A (LDHA), which catalyzes the conversion of pyruvate to lactate, to trigger glycolysis and 5-FU resistance. METTL3/LDHA axis-induced glucose metabolism is a potential therapy target to overcome 5-FU resistance in CRC cells.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	HIF-1 signaling pathway			hsa04066
	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glycolysis
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	For subcutaneous transplanted model, sh-control and sh-METTL3 HCT-116/5-FU cells (5 × 106 per mouse) were diluted in 100ul PBS + 100 ul Matrigel (BD Biosciences, San Jose, CA, USA) and injected subcutaneously in the rear flank fat pad of the nude mice.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[21]
Response Summary	FTO inhibited CRC metastasis both in vitro and in vivo. FTO exerted a tumor suppressive role by inhibiting Metastasis-associated protein MTA1 (MTA1) expression in an m6A-dependent manner. Methylated MTA1 transcripts were recognized by an m6A "reader", insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), which then stabilized its mRNA.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Down regulation
Pathway Response	mRNA surveillance pathway			hsa03015
	RNA degradation			hsa03018
Cell Process	RNA stability
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	LS174T	Colon adenocarcinoma	Homo sapiens	CVCL_1384
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	HCT 15	Colon adenocarcinoma	Homo sapiens	CVCL_0292
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	CW-2	Colon adenocarcinoma	Homo sapiens	CVCL_1151
In-vivo Model	FTO-overexpressing and control cells (2 × 106 suspended in 100 ul PBS) were subcutaneously injected into each mouse.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[21]
Response Summary	FTO inhibited CRC metastasis both in vitro and in vivo. FTO exerted a tumor suppressive role by inhibiting Metastasis-associated protein MTA1 (MTA1) expression in an m6A-dependent manner. Methylated MTA1 transcripts were recognized by an m6A "reader", insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), which then stabilized its mRNA.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015
	RNA degradation			hsa03018
Cell Process	RNA stability
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	LS174T	Colon adenocarcinoma	Homo sapiens	CVCL_1384
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	HCT 15	Colon adenocarcinoma	Homo sapiens	CVCL_0292
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	CW-2	Colon adenocarcinoma	Homo sapiens	CVCL_1151
In-vivo Model	FTO-overexpressing and control cells (2 × 106 suspended in 100 ul PBS) were subcutaneously injected into each mouse.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[10]
Response Summary	WM_Score correlated highly with the regulation of transcription and post-transcriptional events contributing to the development of colorectal cancer. In response to anti-cancer drugs, WM_Score highly negatively correlated (drug sensitive) with drugs which targeted oncogenic related pathways, such as Mitogen-activated protein kinase 1 (MAPK/ERK2/MAPK1), EGFR, and mTOR signaling pathways, positively correlated (drug resistance) with drugs which targeted in apoptosis and cell cycle. Importantly, the WM_Score was associated with the therapeutic efficacy of PD-L1 blockade, suggesting that the development of potential drugs targeting these "writers" to aid the clinical benefits of immunotherapy.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Pathway Response	MAPK signaling pathway			hsa04010
	VEGF signaling pathway			hsa04370
	mTOR signaling pathway			hsa04150
	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
	Apoptosis			hsa04210
Cell Process	Cell apoptosis

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 played a tumor-suppressive role in Colorectal cancer cell proliferation, migration and invasion through Mitogen-activated protein kinase 14 (p38/MAPK14)/ERK pathways, which indicated that METTL3 was a novel marker for CRC carcinogenesis, progression and survival.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	MAPK signaling pathway			hsa04010
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	KM12	Colon carcinoma	Homo sapiens	CVCL_1331

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[22]
Response Summary	METTL3-induced circ1662 promoted colorectal cancer cell invasion and migration by accelerating YAP1 nuclear transport. Circ1662 enhanced CRC invasion and migration depending on YAP1 and Mothers against decapentaplegic homolog 3 (SMAD3). This result implies that circ1662 is a new prognostic and therapeutic marker for CRC metastasis.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Cell invasion
	Cell migration
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
In-vivo Model	BALB/c nude mice (4 weeks old) were acquired from Vital River Laboratory (Beijing, China). HCT116 cells with stable circ1662 expression (2 × 106 in 100 L of PBS) were injected via the tail vein. After 45 days, the mice were sacrificed. The lung metastatic carcinoma specimens were processed into paraffin-embedded sections for subsequent H&E staining and IHC.

In total 4 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[23]
Response Summary	LINRIS blocked K139 ubiquitination of IGF2BP2, maintaining its stability. This process prevented the degradation of IGF2BP2 through the autophagy-lysosome pathway (ALP). The LINRIS-IGF2BP2-Myc proto-oncogene protein (MYC) axis promotes the progression of Colorectal cancer and is a promising therapeutic target. MYC-mediated glycolysis was influenced by the interaction between LINRIS and IGF2BP2.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Autophagy-lysosome pathway
	Ubiquitination
	Glycolysis
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
In-vivo Model	For the orthotopic models, 2 × 106 cells with negative control (NC, sh-NC), sh-1 or sh-2 in 0.5 mL of PBS were subcutaneously injected into the dorsal flank of 2 mice respectively. Then 15 mice were separated into 3 groups (sh-NC, sh-1 and sh-2), of which the tumor pieces were tied to the base of the ceca. The growth of the tumors was monitored every 2 weeks after intraperitoneal injection of D-luciferin with a Xenogen IVIS 100 Bioluminescent Imaging System.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[24]
Response Summary	METTL3 exerted its function through enhancing Myc proto-oncogene protein (MYC) expression, at least partially in an m6A-IGF2BP1-dependent manner. Knockdown of METTL3 suppressed colorectal cancer cell proliferation in vitro and in vivo.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	METTL3 stable knockdown or overexpression HCT116 cells were collected and resuspended at a density of 5 × 106 or 3 × 106 cells per 150 uL PBS.
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[25]
Response Summary	miR-96 antagomir could potentially retard the cancerogenesis in colorectal cancer via AMPK-alpha-2-dependent inhibition of FTO and blocking FTO-mediated m6A modification of Myc proto-oncogene protein (MYC).
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell apoptosis
In-vitro Model	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	RC cells SW480 at logarithmic growth phase were prepared into cell suspension with a concentration of about 1 × 107/100 L, which was then injected into the left axilla of nude mice with a 1 ml syringe to establish a subcutaneous mouse xenograft model. Once the tumor volume reached about 50 mm3, the nude mice were injected with miR-96 antagomir or NC antagomir (10 nmol once every 5 days for 5 weeks). After 5 weeks, the mice were euthanized, after which the subcutaneous transplanted tumor was removed, and weighed.
Experiment 4 Reporting the m6A-centered Disease Response by This Target Gene				[26]
Response Summary	GSK3beta inhibited MZF1 expression by mediating FTO-regulated m6A modification of MZF1 and then decreased the proto-oncogene Myc proto-oncogene protein (MYC) expression, thus hampering CRC cell proliferation.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Cell proliferation
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
In-vivo Model	Twenty-four specific pathogen free female BALB/c nude mice (age: 6 weeks, weight: 15 ~ 18 g) were purchased from Slac Laboratory Animal Co., Ltd., and subcutaneously injected with SW620 cells stably transfected with oe-NC, oe-GSK3-Beta + oe-NC, or oe-GSK3-Beta + oe-c-Myc to establish a subcutaneous xenograft tumour model in nude mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[27]
Response Summary	RBM15 silencing inhibited the CRC growth and metastasis in vitro and in vivo. RBM15 mediated m6A methylation modification of Myeloid differentiation primary response protein MyD88 (MYD88) mRNA in colorectal cancer cells.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	RNA-binding motif protein 15 (RBM15)		WRITER	Regulator Info
Target Regulation	Down regulation
Cell Process	Cell proliferative
	Cell invasive
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[26]
Response Summary	GSK3beta inhibited Myeloid zinc finger 1 (MZF1) expression by mediating FTO-regulated m6A modification of MZF1 and then decreased the proto-oncogene c-Myc expression, thus hampering CRC cell proliferation.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Cell proliferation
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
In-vivo Model	Twenty-four specific pathogen free female BALB/c nude mice (age: 6 weeks, weight: 15 ~ 18 g) were purchased from Slac Laboratory Animal Co., Ltd., and subcutaneously injected with SW620 cells stably transfected with oe-NC, oe-GSK3-Beta + oe-NC, or oe-GSK3-Beta + oe-c-Myc to establish a subcutaneous xenograft tumour model in nude mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[28]
Response Summary	KIAA1429 increased the expression of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) via regulating its mRNA stability in an m6A-dependent manner. More importantly, in vivo experiment showed that depletion of KIAA1429 significantly inhibited colorectal tumor growth.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	NCM460	Normal	Homo sapiens	CVCL_0460
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
In-vivo Model	5.0 × 106 SW480 cells (infected with scr or KIAA1429 shRNA) that suspended in 50 ul PBS and mixed with an equal volume of matrigel were subcutaneously injected in a 6-weeks-old male NOD/SCID (The Jackson Laboratory, Stock No: 001303) mice flank. We started measuring tumor size at the indicated times one week after injection.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[29]
Response Summary	METTL3?dependent m6A methylation was upregulated in CRC to promote the processing of miR?181d?5p by DGCR8. This led to increased miR?181d?5p expression, which inhibited the 5?FU sensitivity of CRC cells by targeting Neurocalcin-delta (NCALD).
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Fluorouracil		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
In-vivo Model	A tumor-bearing model was established by subcutaneously injecting 100 ul HT29 cells (5×106) followed by an intravenous injection of CAFs-derived exosomes (50 ug/mouse every three days) into the tail vein of the mice. An intraperitoneal injection of 5-FU (50 mg/kg, every week) was administered on day 12.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[30]
Response Summary	The critical modulation network underlying m6A readers stabilizes lncRNAs, and they jointly promote mitochondrial energy metabolism in the pathogenesis of colorectal cancer. N6-methyladenosine reader stabilizes the ZFAS1/OLA1 axis. Thus, direct interaction between the KH3-4 domain of IMP2 and ZFAS1 where IMP2 serves as a reader for m6A-modified ZFAS1 and promotes the RNA stability of ZFAS1 is critical for CRC development.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Warburg effect
	Mitochondrial energy metabolism
In-vitro Model	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HIEC (Normal intestinal epithelial cells)
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[18]
Response Summary	The study highlights a robust correlation between the level of cancer stemness and traits related to tumor heterogeneity, including the immune microenvironment, TMB, and the expression of m6A RNA methylation regulatory factors in colorectal cancer cells. A three-gene prognostic signature (PCNA-interacting partner (PARPBP), KNSTRN, and KIF2C) was explored together with specific clinical features to construct a nomogram, which was successfully validated in an external cohort.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[15]
Response Summary	Targeting FTO significantly suppresses cancer cell growth and enhances chemotherapy sensitivity, which not only mediating the balance of intracellular ROS by regulating G6PD expression, but also maintaining genome instability by regulating Poly [ADP-ribose] polymerase 1 (PARP1) expression. These findings shed light on new molecular mechanisms of CRC development and treatments mediated by m6A modification.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Glutathione metabolism			hsa00480
In-vitro Model	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	For CDX model, nude mice (female, 4-6-week-old) were subcutaneously injected with 5 × 106 HCT116 cells on the both flank. For PDX model, the patient tumors were divided into small pieces and then inoculated on both flank of nude mice. For knockdown FTO mice model, FTO mice model, two weeks after inoculation, the shFTO#3 lenti-virus injected into the tumor for three consecutive days. For combined medication mice model, intraperitoneal injection of Rhein and Olaparib was started one week after inoculation

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[10]
Response Summary	WM_Score correlated highly with the regulation of transcription and post-transcriptional events contributing to the development of colorectal cancer. In response to anti-cancer drugs, WM_Score highly negatively correlated (drug sensitive) with drugs which targeted oncogenic related pathways, such as MAPK, EGFR, and mTOR signaling pathways, positively correlated (drug resistance) with drugs which targeted in apoptosis and cell cycle. Importantly, the WM_Score was associated with the therapeutic efficacy of Programmed cell death 1 ligand 1 (CD274/PD-L1) blockade, suggesting that the development of potential drugs targeting these "writers" to aid the clinical benefits of immunotherapy.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Pathway Response	MAPK signaling pathway			hsa04010
	VEGF signaling pathway			hsa04370
	mTOR signaling pathway			hsa04150
	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Cell apoptosis

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[31]
Response Summary	m6A and METTL3 levels were substantially elevated in colorectal carcinoma(CRC) tissues, METTL3 knockdown substantially reduced the m6A level of Protein crumbs homolog 3 (CRB3), and inhibited the degradation of CRB3 mRNA to increase CRB3 expression. METTL3 regulated the progression of CRC by regulating the m6A-CRB3-Hippo pathway.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	FHC	Normal	Homo sapiens	CVCL_3688
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547

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

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[32]
Response Summary	METTL3-catalyzed m6A modification in CRC tumorigenesis, wherein it facilitates CRC tumor growth and metastasis through suppressing Protein yippee-like 5 (YPEL5) expression in an m6A-YTHDF2-dependent manner.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	NCM460	Normal	Homo sapiens	CVCL_0460
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
In-vivo Model	For the xenograft model, METTL3 stable overexpressed SW620 cells (1 × 107) or control cells were subcutaneously injected into the right axilla of the female anesthetized BALB/C nude mice (4-6 weeks old, 18-20 g, four mice per group), respectively. The body weight and tumor volumes (length × width2 × 0.5) were measured twice a week. After 21 days, all mice were sacrificed and tumors were surgically removed for hematoxylin-eosin (H&E) staining.For the metastasis model, MTTL3 stable overexpressed SW620 cells (1 × 106) or control cells were injected into the exposed spleen of the anesthetized BALB/C nude mice, respectively. After 21 days, liver metastases were carefully detected using a fluorescent stereoscope and embedded for H&E staining.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[32]
Response Summary	METTL3-catalyzed m6A modification in CRC tumorigenesis, wherein it facilitates CRC tumor growth and metastasis through suppressing Protein yippee-like 5 (YPEL5) expression in an m6A-YTHDF2-dependent manner.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	NCM460	Normal	Homo sapiens	CVCL_0460
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
In-vivo Model	For the xenograft model, METTL3 stable overexpressed SW620 cells (1 × 107) or control cells were subcutaneously injected into the right axilla of the female anesthetized BALB/C nude mice (4-6 weeks old, 18-20 g, four mice per group), respectively. The body weight and tumor volumes (length × width2 × 0.5) were measured twice a week. After 21 days, all mice were sacrificed and tumors were surgically removed for hematoxylin-eosin (H&E) staining.For the metastasis model, MTTL3 stable overexpressed SW620 cells (1 × 106) or control cells were injected into the exposed spleen of the anesthetized BALB/C nude mice, respectively. After 21 days, liver metastases were carefully detected using a fluorescent stereoscope and embedded for H&E staining.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[33]
Response Summary	In colorectal cancer, n6-methyladenosine (m6A) subunit METTL3 increased PTTG3P expression by influencing its stability, while insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) could identify Putative pituitary tumor-transforming gene 3 protein (PTTG3P) m6A methylation status and bind to it.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Cell proliferation and suppression of apoptosis
In-vitro Model	FHC	Normal	Homo sapiens	CVCL_3688
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	NCM460	Normal	Homo sapiens	CVCL_0460
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	Indicated cells (1 × 107) were subcutaneously injected into 4-week-old male nude mice. Tumor volume was measured every 5 days.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[33]
Response Summary	In colorectal cancer, n6-methyladenosine (m6A) subunit METTL3 increased PTTG3P expression by influencing its stability, while insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) could identify Putative pituitary tumor-transforming gene 3 protein (PTTG3P) m6A methylation status and bind to it.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Cell proliferation and suppression of apoptosis
In-vitro Model	FHC	Normal	Homo sapiens	CVCL_3688
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	NCM460	Normal	Homo sapiens	CVCL_0460
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	Indicated cells (1 × 107) were subcutaneously injected into 4-week-old male nude mice. Tumor volume was measured every 5 days.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[34]
Response Summary	METTL3 augmented 5?FU?induced DNA damage and overcame 5?FU?resistance in HCT?8R cells, which could be mimicked by inhibition of RAD51-associated protein 1 (RAD51AP1). The present study revealed that the METTL3/RAD51AP1 axis plays an important role in the acquisition of 5?FU resistance in CRC.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Fluorouracil		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[35]
Response Summary	IGF2BP2 activates the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2) by recognizing the m6A of YAP, thus affecting the cell cycle of colorectal cancer, inhibiting cell apoptosis, and promoting proliferation.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Temozolomide		Approved	Drug Info
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Cell apoptosis
In-vitro Model	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	IGF2BP2 activates the expression of ErbB2 by recognizing the m6A of YAP, thus affecting the cell cycle of CRC, inhibiting cell apoptosis, and promoting proliferation.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[36]
Response Summary	YTHDF1 promotes cell growth in CRC cell lines and primary organoids and lung and liver metastasis in vivo. YTHDF1 binds to m6A sites of Rho guanine nucleotide exchange factor 2 (ARHGEF2) messenger RNA, resulting in enhanced translation of ARHGEF2.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	SW1116	Colon adenocarcinoma	Homo sapiens	CVCL_0544
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	LS180	Colon adenocarcinoma	Homo sapiens	CVCL_0397
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[37]
Response Summary	N6-methyladenosine modification of RNA cytosine C(5)-methyltransferase NSUN2 (NSUN2) modulates cytoplasmic export and stabilizes HMGA2 to promote Colorectal carcinoma LM. By forming a circNSUN2/IGF2BP2/HMGA2 RNA-protein ternary complex in the cytoplasm, circNSUN2 enhances the stability of HMGA2 mRNA to promote CRC metastasis progression.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cells invasion
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	SW1116	Colon adenocarcinoma	Homo sapiens	CVCL_0544
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	2 × 106 cells suspended in 40 uL PBS were injected into the inferior hemispleen into each 6-week-old BALB/c nude mouse.

In total 5 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Asparagine inhibitor		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Asparagine inhibitor		Approved	Drug Info
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Serine/threonine-protein kinase mTOR (MTOR) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Chloroquine		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Experiment 4 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Serine/threonine-protein kinase mTOR (MTOR) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Meclofenamate sodium		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Experiment 5 Reporting the m6A-centered Disease Response by This Target Gene				[10]
Response Summary	WM_Score correlated highly with the regulation of transcription and post-transcriptional events contributing to the development of colorectal cancer. In response to anti-cancer drugs, WM_Score highly negatively correlated (drug sensitive) with drugs which targeted oncogenic related pathways, such as MAPK, EGFR, and Serine/threonine-protein kinase mTOR (MTOR) signaling pathways, positively correlated (drug resistance) with drugs which targeted in apoptosis and cell cycle. Importantly, the WM_Score was associated with the therapeutic efficacy of PD-L1 blockade, suggesting that the development of potential drugs targeting these "writers" to aid the clinical benefits of immunotherapy.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Pathway Response	MAPK signaling pathway			hsa04010
	VEGF signaling pathway			hsa04370
	mTOR signaling pathway			hsa04150
	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Cell apoptosis

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[18]
Response Summary	The study highlights a robust correlation between the level of cancer stemness and traits related to tumor heterogeneity, including the immune microenvironment, TMB, and the expression of m6A RNA methylation regulatory factors in colorectal cancer cells. A three-gene prognostic signature (PARPBP, Small kinetochore-associated protein (KNSTRN), and KIF2C) was explored together with specific clinical features to construct a nomogram, which was successfully validated in an external cohort.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[38]
Response Summary	Overexpression of LINC01605, regulated by SMYD2-EP300-mediated H3K27ac and H3K4me3 modifications, bound to METTL3 protein to promote m6A modification of Spectrin beta, non-erythrocytic 2 (SPTBN2) mRNA, leading to the development of colorectal cancer.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation and metastasis
	Cell apoptosis
In-vitro Model	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
In-vivo Model	The growth of CC cells in vivo was examined by subcutaneous injection of LoVo cells or Caco-2 cells into NSG mice, while the metastatic ability of cells in vivo by intracardiac injection into mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[39]
Response Summary	METTL3/miR-1246/Sprouty-related, EVH1 domain-containing protein 2 (SPRED2) axis plays an important role in tumor metastasis and provides a new m6A modification pattern in Colorectal cancer development.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	MAPK signaling pathway			hsa04010
Cell Process	Cell migration and invasion
In-vitro Model	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	NCM460	Normal	Homo sapiens	CVCL_0460
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
In-vivo Model	The spleen in the upper left lateral abdomen of the anesthetized mice were exposed, 106 cells suspended in 20 uL phosphate-buffered saline (PBS) were injected into the distal tip of the spleen. After injection, replacing the spleen, and closing the incision.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[40]
Response Summary	The colorimetric m6A quantification strategy revealed that Staphylococcal nuclease domain-containing protein 1 (SND1) could alter m6A levels in colorectal cancer cell lines.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Cell Process	RNA stability
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[41]
Response Summary	2-polarized tumor-associated macrophages enabled the oxaliplatin resistance via the elevation of METTL3-mediated m6A modification in Colorectal Cancer cells. Furthermore, they found that TNF receptor-associated factor 5 (TRAF5) contributes to the METTL3-triggered OX resistance in CRC cells.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Oxaliplatin		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
In-vivo Model	HCT-116 cells (3 × 105 cells in 200 uL of saline) were subcutaneously injected into the nude mice to establish xenograft tumors. After 10 days, 10 mg/kg OX or saline was intraperitoneally injected (n = 5 for each group). Si-METTL3 or si-TRAF5 (10 nmol/20 g body weight) was injected twice intratumorally before the start of OX treatment. The mice were examined every 2 days and sacrificed 4 weeks after the OX treatment.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[42]
Response Summary	MIR100HG and hnRNPA2B1 interact to control the transcriptional activity of Wnt signaling in CRC via regulation of Transcription factor 7-like 2 (TCF7L2) mRNA stability. These findings identified MIR100HG as a potent EMT inducer in CRC that contribute to cetuximab resistance and metastasis by activation of a MIR100HG/hnRNPA2B1/TCF7L2 feedback loop.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Cetuximab		Approved	Drug Info
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	VACO 9P	Rectal adenocarcinoma	Homo sapiens	CVCL_5413
	T84	Colon adenocarcinoma	Homo sapiens	CVCL_0555
	SW948	Colon adenocarcinoma	Homo sapiens	CVCL_0632
	SW837	Rectal adenocarcinoma	Homo sapiens	CVCL_1729
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW48	Colon adenocarcinoma	Homo sapiens	CVCL_1724
	SW403	Colon adenocarcinoma	Homo sapiens	CVCL_0545
	SW1116	Colon adenocarcinoma	Homo sapiens	CVCL_0544
	SK-CO-1	Colon adenocarcinoma	Homo sapiens	CVCL_0626
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	NCI-H716	Cecum adenocarcinoma	Homo sapiens	CVCL_1581
	NCI-H508	Cecum adenocarcinoma	Homo sapiens	CVCL_1564
	LS174T	Colon adenocarcinoma	Homo sapiens	CVCL_1384
	LS123	Colon adenocarcinoma	Homo sapiens	CVCL_1383
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	LIM2405	Cecum adenocarcinoma	Homo sapiens	CVCL_4437
	LIM1215	Colon adenocarcinoma	Homo sapiens	CVCL_2574
	HuTu 80	Duodenal adenocarcinoma	Homo sapiens	CVCL_1301
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	HCT 15	Colon adenocarcinoma	Homo sapiens	CVCL_0292
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	GEO	Colon carcinoma	Homo sapiens	CVCL_0271
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	DiFi	Colorectal carcinoma	Homo sapiens	CVCL_6895
	COLO 320DM	Colon adenocarcinoma	Homo sapiens	CVCL_0219
	COLO 205	Colon adenocarcinoma	Homo sapiens	CVCL_0218
	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
In-vivo Model	Established subcutaneous xenografts in athymic nude mice with MIR100HGKOE4 CC-CR cells transduced with a luciferase-expressing lentiviral vector and then treated the mice with cetuximab.

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Transcription factor ISGF-3 components p91/p84 (Stat1) and Irf1 mRNA via Ythdf2.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 106 CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Transcription factor ISGF-3 components p91/p84 (Stat1) and Irf1 mRNA via Ythdf2.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 106 CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Transcription factor ISGF-3 components p91/p84 (Stat1) and Irf1 mRNA via Ythdf2.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 106 CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[43]
Response Summary	METTL3, acting as an oncogene, maintained Transcription factor SOX-2 (SOX2) expression through an m6A-IGF2BP2-dependent mechanism in CRC cells, and indicated a potential biomarker panel for prognostic prediction in Colorectal carcinoma.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Signaling pathways regulating pluripotency of stem cells			hsa04550
Cell Process	Cell self-renewal
	Stem cell frequency
	Cell migration
In-vitro Model	CCD-112CoN	Normal	Homo sapiens	CVCL_6382
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 15	Colon adenocarcinoma	Homo sapiens	CVCL_0292
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	LS174T	Colon adenocarcinoma	Homo sapiens	CVCL_1384
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[43]
Response Summary	METTL3, acting as an oncogene, maintained Transcription factor SOX-2 (SOX2) expression through an m6A-IGF2BP2-dependent mechanism in CRC cells, and indicated a potential biomarker panel for prognostic prediction in Colorectal carcinoma.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Signaling pathways regulating pluripotency of stem cells			hsa04550
Cell Process	Cell self-renewal
	Stem cell frequency
	Cell migration
In-vitro Model	CCD-112CoN	Normal	Homo sapiens	CVCL_6382
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 15	Colon adenocarcinoma	Homo sapiens	CVCL_0292
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	LS174T	Colon adenocarcinoma	Homo sapiens	CVCL_1384
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[44]
Response Summary	METTL14 inhibited colorectal cancer malignant process partly through Transcription factor SOX-4 (SOX4)-mediated EMT process and PI3K/Akt signals.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell migration
	Cell invasion
	Cell metastasis
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	NCM460	Normal	Homo sapiens	CVCL_0460
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	2 × 106 transfected HCT116 cells in 0.2 ml PBS were injected into the tail vein of nude mice which were randomly divided into nine groups (eight mice per group).

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[35]
Response Summary	IGF2BP2 activates the expression of ErbB2 by recognizing the m6A of Transcriptional coactivator YAP1 (YAP1), thus affecting the cell cycle of colorectal cancer, inhibiting cell apoptosis, and promoting proliferation.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Temozolomide		Approved	Drug Info
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Cell apoptosis
In-vitro Model	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	IGF2BP2 activates the expression of ErbB2 by recognizing the m6A of YAP, thus affecting the cell cycle of CRC, inhibiting cell apoptosis, and promoting proliferation.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[22]
Response Summary	METTL3-induced circ1662 promoted colorectal cancer cell invasion and migration by accelerating Transcriptional coactivator YAP1 (YAP1) nuclear transport. Circ1662 enhanced CRC invasion and migration depending on YAP1 and SMAD3. This result implies that circ1662 is a new prognostic and therapeutic marker for CRC metastasis.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Cell invasion
	Cell migration
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
In-vivo Model	BALB/c nude mice (4 weeks old) were acquired from Vital River Laboratory (Beijing, China). HCT116 cells with stable circ1662 expression (2 × 106 in 100 L of PBS) were injected via the tail vein. After 45 days, the mice were sacrificed. The lung metastatic carcinoma specimens were processed into paraffin-embedded sections for subsequent H&E staining and IHC.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[45]
Response Summary	Translocation protein SEC62 (SEC62) upregulated by the METTL3-mediated m6A modification promotes the stemness and chemoresistance of colorectal cancer by binding to beta-catenin and enhancing Wnt signalling. Depletion of Sec62 sensitized the CRC cells to 5-Fu or oxaliplatin treatment.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Fluorouracil		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Protein degradation
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
In-vivo Model	DLD-1 cells were subcutaneously implanted into 4-6 weeks old female nude mice. When tumors reached a size of about 50 mm3, the nude mice were randomly divided into 6 groups.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[45]
Response Summary	Translocation protein SEC62 (SEC62) upregulated by the METTL3-mediated m6A modification promotes the stemness and chemoresistance of colorectal cancer by binding to beta-catenin and enhancing Wnt signalling. Depletion of Sec62 sensitized the CRC cells to 5-Fu or oxaliplatin treatment.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Oxaliplatin		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Protein degradation
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
In-vivo Model	DLD-1 cells were subcutaneously implanted into 4-6 weeks old female nude mice. When tumors reached a size of about 50 mm3, the nude mice were randomly divided into 6 groups.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[46]
Response Summary	YTHDF3 was highly expressed in oxaliplatin-resistant (OXAR) CRC tissues and cells. YTHDF3 as a novel hallmark and revealed the molecular mechanism of YTHDF3 on gene translation via coordination with Tyrosine-protein kinase EIF2AK2 (eIF2AK2/p68) in OXAR CRC cells.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	YTH domain-containing family protein 3 (YTHDF3)		READER	Regulator Info
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	HCoEpiC (Healthy colon epithelial HCoEpiC cells)
	FHC	Normal	Homo sapiens	CVCL_3688

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	The U4/U6 small nuclear ribonucleoprotein Prp31 (PRPF31/RP11)/hnRNPA2B1/mRNA complex accelerated the mRNA degradation of two E3 ligases, Siah1 and Fbxo45, and subsequently prevented the proteasomal degradation of Zeb1. m6A can regulate the expression of RP11, further, RP11 regulated Siah1-Fbxo45/Zeb1 was involved in the development of Colorectal cancer.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Proteasome			hsa03050
Cell Process	Proteasomal degradation
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 15	Colon adenocarcinoma	Homo sapiens	CVCL_0292
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
In-vivo Model	HCT-15 RP11 stable overexpression or control cells (2 × 106 per mouse) diluted in 100 uL normal medium + 100 uL Matrigel (BD Biosciences) were subcutaneously injected into immunodeficient mice to investigate tumour growth.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[47]
Response Summary	METTL3 upregulated Urokinase-type plasminogen activator (PLAU) mRNA in an m6A-dependent manner, and then participated in MAPK/ERK pathway to promote angiogenesis and metastasis in CRC.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	MAPK signaling pathway			hsa04010
In-vitro Model	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
In-vivo Model	1 × 106 cells in 100 uL PBS (shMETTL3-1 or shNC) were respectively injected into each mouse through the tail vein. Pulmonary metastases were monitored after fourteen days using the imaging system (IVIS) Spectrum (PerkinElmer, USA).

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	EphA2 and Vascular endothelial growth factor A (VEGFA) targeted by METTL3 via different IGF2BP-dependent mechanisms were found to promote vasculogenic mimicry (VM) formation via PI3K/AKT/mTOR and ERK1/2 signaling in CRC.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Pathway Response	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	NCM460	Normal	Homo sapiens	CVCL_0460
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
In-vivo Model	A total of 8 × 106 wild-type (WT) or METTL3-knockdown cells were injected into the dorsal flanks of 6-week-old nude mice. Seven mice were randomly selected to calculate the volume according to the following formula: V = (width2 × length)/2. Mice were euthanized three weeks after injection and tumors removed, weighed, fixed, and embedded for immunohistochemical analysis.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	EphA2 and Vascular endothelial growth factor A (VEGFA) targeted by METTL3 via different IGF2BP3-dependent mechanisms were found to promote vasculogenic mimicry (VM) formation via PI3K/AKT/mTOR and ERK1/2 signaling in CRC.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	NCM460	Normal	Homo sapiens	CVCL_0460
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
In-vivo Model	A total of 8 × 106 wild-type (WT) or METTL3-knockdown cells were injected into the dorsal flanks of 6-week-old nude mice. Seven mice were randomly selected to calculate the volume according to the following formula: V = (width2 × length)/2. Mice were euthanized three weeks after injection and tumors removed, weighed, fixed, and embedded for immunohistochemical analysis.
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	EphA2 and Vascular endothelial growth factor A (VEGFA) targeted by METTL3 via different IGF2BP2-dependent mechanisms were found to promote vasculogenic mimicry (VM) formation via PI3K/AKT/mTOR and ERK1/2 signaling in CRC.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	NCM460	Normal	Homo sapiens	CVCL_0460
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
In-vivo Model	A total of 8 × 106 wild-type (WT) or METTL3-knockdown cells were injected into the dorsal flanks of 6-week-old nude mice. Seven mice were randomly selected to calculate the volume according to the following formula: V = (width2 × length)/2. Mice were euthanized three weeks after injection and tumors removed, weighed, fixed, and embedded for immunohistochemical analysis.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[48]
Response Summary	KIAA1429 plays an oncogenic role in CRC cells by inhibiting the expression of Wee1-like protein kinase (WEE1) in an m6A-independent manner and is associated with poor survival in CRC patients.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	The RP11/hnRNPA2B1/mRNA complex accelerated the mRNA degradation of two E3 ligases, Siah1 and Fbxo45, and subsequently prevented the proteasomal degradation of Zinc finger E-box-binding homeobox 1 (ZEB1). m6A can regulate the expression of RP11, further, RP11 regulated Siah1-Fbxo45/Zeb1 was involved in the development of Colorectal cancer.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Proteasome			hsa03050
Cell Process	Proteasomal degradation
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 15	Colon adenocarcinoma	Homo sapiens	CVCL_0292
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
In-vivo Model	HCT-15 RP11 stable overexpression or control cells (2 × 106 per mouse) diluted in 100 uL normal medium + 100 uL Matrigel (BD Biosciences) were subcutaneously injected into immunodeficient mice to investigate tumour growth.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[49]
Response Summary	METTL3 acts as a critical m6A methyltransferase capable of facilitating colorectal cancer(CRC) progression, and revealed a novel mechanism by which METTL3 promotes CRC cell proliferation and invasion via stabilizing Zinc finger protein SNAI1 (SNAI1) mRNA in an m6A-dependent manner.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Adherens junction			hsa04520
Cell Process	Cell proliferation
	Cell invasion
In-vitro Model	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	NCM460	Normal	Homo sapiens	CVCL_0460
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HIEC-6	Normal	Homo sapiens	CVCL_6C21
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HEK293T	Normal	Homo sapiens	CVCL_0063

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[50]
Response Summary	A new mechanism for m6A-induced decay of Growth arrest specific 5 (GAS5) on YAP signaling in progression of Colorectal cancer which offers a promising approach for CRC treatment. LncRNA GAS5 expressions is negatively correlated with YAP and YTHDF3 protein levels in tumors from CRC patients.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	YTH domain-containing family protein 3 (YTHDF3)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Ubiquitination degradation
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	LS174T	Colon adenocarcinoma	Homo sapiens	CVCL_1384
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[51]
Response Summary	The increased LBX2 antisense RNA 1 (LBX2-AS1) in CRC was mediated by METTL3-dependent m6A methylation. LBX2-AS1 serves as a therapeutic target and predictor of 5-FU benefit in colorectal cancer patients.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Fluorouracil		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[52]
Response Summary	Overexpression of METTL3 upregulates Long intergenic non-protein coding RNA 2598 (LINC02598/RP11) expression in colorectal cancer cells. Overexpression of ALKBH5 downregulates RP11 expression.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Down regulation
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[52]
Response Summary	Overexpression of METTL3 upregulates Long intergenic non-protein coding RNA 2598 (LINC02598/RP11) expression in colorectal cancer cells. Overexpression of ALKBH5 downregulates RP11 expression.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Ubiquitination degradation
In-vitro Model	HCT 15	Colon adenocarcinoma	Homo sapiens	CVCL_0292
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	NCM460	Normal	Homo sapiens	CVCL_0460

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[17]
Response Summary	Long intergenic non-protein coding RNA 460 (LINC00460) is a novel oncogene of colorectal cancer through interacting with IGF2BP2 and DHX9 and bind to the m6A modified HMGA1 mRNA to enhance the HMGA1 mRNA stability. The N6-methyladenosine (m6A) modification of HMGA1 mRNA by METTL3 enhanced HMGA1 expression in CRC.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Cell Process	mRNA stability
	Epithelial-mesenchymal transition
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	FHC	Normal	Homo sapiens	CVCL_3688
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	Groups of HCT116-Luc-shCtrl, HCT116-Luc-shLINC00460, and HCT116-Luc-shLINC00460 + HMGA1 cells (5 × 106) were injected subcutaneously into the flanks of mice correspondingly.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[53]
Response Summary	ALKBH5 knockdown suppressed malignant behavior of colon cancer partially through Nuclear paraspeckle assembly transcript 1 (NEAT1) by demethylation in vitro and vivo, suggesting that ALKBH5-NEAT1 axis is a potential therapeutic target for colon cancer treatment.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation and migration
	Cell apoptosis
In-vitro Model	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	HIEC (Normal intestinal epithelial cells)
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	To establish xenograft model, RKO cells (1 × 107) tansduced with si-control (si-NC) or si-ALKBH5 or si-ALKBH5+NEAT1 were injected subcutaneously into the right flank of the nude mice (n = 6 each group) every 5 days for 4 times.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[54]
Response Summary	In colorectal cancer, knockdown of METTL14 substantially abolished m6A level of X inactive specific transcript (XIST) and augmented XIST expression. m6A-methylated XIST was recognized by YTHDF2, a m6A reader protein, to mediate the degradation of XIST.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Cell Process	Tumorigenicity and metastasis
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	NCM460	Normal	Homo sapiens	CVCL_0460
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	For liver metastasis model, mice were anaesthetized and an incision was made through the skin and peritoneum to expose the spleen. 1 × 106 HCT116 cells were injected into the spleen (n = 4 each group).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[54]
Response Summary	In colorectal cancer, knockdown of METTL14 substantially abolished m6A level of X inactive specific transcript (XIST) and augmented XIST expression. m6A-methylated XIST was recognized by YTHDF2, a m6A reader protein, to mediate the degradation of XIST.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Tumorigenicity and metastasis
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	NCM460	Normal	Homo sapiens	CVCL_0460
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	For liver metastasis model, mice were anaesthetized and an incision was made through the skin and peritoneum to expose the spleen. 1 × 106 HCT116 cells were injected into the spleen (n = 4 each group).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[30]
Response Summary	The critical modulation network underlying m6A readers stabilizes lncRNAs, and they jointly promote mitochondrial energy metabolism in the pathogenesis of colorectal cancer. N6-methyladenosine reader stabilizes the ZFAS1/OLA1 axis. Thus, direct interaction between the KH3-4 domain of IMP2 and ZFAS1 where IMP2 serves as a reader for m6A-modified ZFAS1 and promotes the RNA stability of ZFAS1 is critical for CRC development.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Warburg effect
	Mitochondrial energy metabolism
In-vitro Model	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HIEC (Normal intestinal epithelial cells)
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[39]
Response Summary	METTL3/microRNA 1246 (MIR1246)/SPRED2 axis plays an important role in tumor metastasis and provides a new m6A modification pattern in Colorectal cancer development.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	MAPK signaling pathway			hsa04010
Cell Process	Cell migration and invasion
In-vitro Model	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	NCM460	Normal	Homo sapiens	CVCL_0460
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
In-vivo Model	The spleen in the upper left lateral abdomen of the anesthetized mice were exposed, 106 cells suspended in 20 uL phosphate-buffered saline (PBS) were injected into the distal tip of the spleen. After injection, replacing the spleen, and closing the incision.

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 plays an antitumor role in colorectal cancer by modulating the FOXO3/microRNA 21 (MIR21)/SPRY2 axis, which not only suggests a regulatory effect between ALKBH5 and FOXO3, but also provides a new therapeutic direction for colorectal cancer.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Pathway Response	FoxO signaling pathway			hsa04068
In-vitro Model	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	FHC	Normal	Homo sapiens	CVCL_3688
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[55]
Response Summary	METTL14 suppressed Colorectal cancer cell growth, migration, and invasion via the microRNA 375 (MIR375)/YAP1 and miR-375/SP1 pathways.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Cell growth and metastasis
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	FHC	Normal	Homo sapiens	CVCL_3688
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	Six-week-old BALB/c nude mice were purchased from the College of Veterinary Medicine, Yang Zhou University. For the xenografted tumor model, 1 × 107 HCT116 cells in 0.2 mL PBS were subcutaneously injected into BALB/c nude mice, which were randomly divided into four groups (six mice per group). The volume of the tumors was calculated with the following equation: V = 0.5 × (length × width2). For metastasis experiments, 2 × 106 cells in 0.2 mL PBS were injected into the tail vein of nude mice, which were randomly divided into four groups (six mice per group).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[42]
Response Summary	Mir-100-let-7a-2-mir-125b-1 cluster host gene (MIR100HG) and hnRNPA2B1 interact to control the transcriptional activity of Wnt signaling in CRC via regulation of TCF7L2 mRNA stability. These findings identified MIR100HG as a potent EMT inducer in CRC that will contribute to cetuximab resistance and metastasis by activation of a MIR100HG/hnRNPA2B1/TCF7L2 feedback loop.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Cetuximab		Approved	Drug Info
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	VACO 9P	Rectal adenocarcinoma	Homo sapiens	CVCL_5413
	T84	Colon adenocarcinoma	Homo sapiens	CVCL_0555
	SW948	Colon adenocarcinoma	Homo sapiens	CVCL_0632
	SW837	Rectal adenocarcinoma	Homo sapiens	CVCL_1729
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW48	Colon adenocarcinoma	Homo sapiens	CVCL_1724
	SW403	Colon adenocarcinoma	Homo sapiens	CVCL_0545
	SW1116	Colon adenocarcinoma	Homo sapiens	CVCL_0544
	SK-CO-1	Colon adenocarcinoma	Homo sapiens	CVCL_0626
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	NCI-H716	Cecum adenocarcinoma	Homo sapiens	CVCL_1581
	NCI-H508	Cecum adenocarcinoma	Homo sapiens	CVCL_1564
	LS174T	Colon adenocarcinoma	Homo sapiens	CVCL_1384
	LS123	Colon adenocarcinoma	Homo sapiens	CVCL_1383
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	LIM2405	Cecum adenocarcinoma	Homo sapiens	CVCL_4437
	LIM1215	Colon adenocarcinoma	Homo sapiens	CVCL_2574
	HuTu 80	Duodenal adenocarcinoma	Homo sapiens	CVCL_1301
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	HCT 15	Colon adenocarcinoma	Homo sapiens	CVCL_0292
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	GEO	Colon carcinoma	Homo sapiens	CVCL_0271
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	DiFi	Colorectal carcinoma	Homo sapiens	CVCL_6895
	COLO 320DM	Colon adenocarcinoma	Homo sapiens	CVCL_0219
	COLO 205	Colon adenocarcinoma	Homo sapiens	CVCL_0218
	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
In-vivo Model	Established subcutaneous xenografts in athymic nude mice with MIR100HGKOE4 CC-CR cells transduced with a luciferase-expressing lentiviral vector and then treated the mice with cetuximab.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[29]
Response Summary	METTL3?dependent m6A methylation was upregulated in CRC to promote the processing of miR?181d?5p by DGCR8. This led to increased hsa-miR-181d-5p expression, which inhibited the 5?FU sensitivity of CRC cells by targeting NCALD.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Fluorouracil		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
In-vivo Model	A tumor-bearing model was established by subcutaneously injecting 100 ul HT29 cells (5×106) followed by an intravenous injection of CAFs-derived exosomes (50 ug/mouse every three days) into the tail vein of the mice. An intraperitoneal injection of 5-FU (50 mg/kg, every week) was administered on day 12.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[56]
Response Summary	hsa_circ_0000677 and its downstream target ABCC1 were upregulated in CRC cells, induced by the METTL3-mediated m6 A modification of circ_0000677 and SUMO1-mediated SUMOylation of METTL3. This work provided a new strategy for the therapeutic treatment of CRC.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	NCM460	Normal	Homo sapiens	CVCL_0460
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 15	Colon adenocarcinoma	Homo sapiens	CVCL_0292
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
In-vivo Model	For the tumor xenograft, mice were randomly divided into three groups with four mice for each group. Then, 1 × 106 cells after indicated treatment were harvested and resuspended in 50 ul of PBS. Then the cells were subcutaneously injected into the right front flank of each mouse.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[22]
Response Summary	METTL3-induced Circ_1662 promoted colorectal cancer cell invasion and migration by accelerating YAP1 nuclear transport. Circ1662 enhanced CRC invasion and migration depending on YAP1 and SMAD3. This result implies that circ1662 is a new prognostic and therapeutic marker for CRC metastasis.
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Cell invasion
	Cell migration
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
In-vivo Model	BALB/c nude mice (4 weeks old) were acquired from Vital River Laboratory (Beijing, China). HCT116 cells with stable circ1662 expression (2 × 106 in 100 L of PBS) were injected via the tail vein. After 45 days, the mice were sacrificed. The lung metastatic carcinoma specimens were processed into paraffin-embedded sections for subsequent H&E staining and IHC.