General Information of the Disease (ID: M6ADIS0057)
Name
Gastric cancer
ICD
ICD-11: 2B72
Full List of Target Gene(s) of This m6A-centered Disease Response
A disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS9)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary METTL3 facilitates GC progression through the A disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS9)-mediated PI3K/AKT pathway.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Down regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process RNA stability
In-vitro Model HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model For the formation of xenograft tumors, 5 × 106 AGS cells mixed in Matrigel (BD Biosciences, Franklin Lakes, NJ, USA) were subcutaneously injected into BALB/c nude mice (5-week-old male).
Actin, aortic smooth muscle (ACTA2)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [2]
Response Summary METTL3 knockdown decreased Actin, aortic smooth muscle (ACTA2) muscle actin. Taken together, our finding revealed that m6A methylation writer METTL3 serve as an oncogene in tumorigenesis of Gastric cancer.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Cell Process Cell proliferation
In-vitro Model BGC-823 Gastric carcinoma Homo sapiens CVCL_3360
GES-1 Normal Homo sapiens CVCL_EQ22
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
Apoptosis regulator BAX (BAX)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [3]
Response Summary Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Bcl2 and increased Apoptosis regulator BAX (BAX) and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors p70S6K and Cyclin D1.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Down regulation
Pathway Response Apoptosis hsa04210
PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
Apoptosis regulator Bcl-2 (BCL2)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [3]
Response Summary Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Apoptosis regulator Bcl-2 (BCL2) and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors p70S6K and Cyclin D1.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response Apoptosis hsa04210
PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
Basic leucine zipper transcriptional factor ATF-like 2 (BATF2)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [4]
Response Summary N6-methyladenosine (m6A) modification of Basic leucine zipper transcriptional factor ATF-like 2 (BATF2) mRNA by METTL3 repressed its expression in gastric cancer.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Down regulation
Pathway Response p53 signaling pathway hsa04115
In-vitro Model SNU-216 Gastric tubular adenocarcinoma Homo sapiens CVCL_3946
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
In-vivo Model A total of 5 × 106 stably transfected HGC-27 cells were subcutaneously injected into the right axillary fossa of nude mice. Tumor volume was measured every 3 days and calculated with the following formula: V = (L × W2)/2 cm2 (V, tumor volume; L, length; W, width). The mice were sacrificed at 3-4 weeks after injection, and the tumors were weighed. For the lung metastasis model, 5 × 106 stably transfected HGC-27 cells were injected into the tail veins of nude mice. Forty-five days later, the mice were sacrificed, and the lungs were dissected to examine the histopathological metastatic loci. The peritoneal dissemination ability of GC cells was evaluated via intraperitoneal injection. A total of 5 × 106 stably transfected HGC-27 cells in 500 uL of PBS were injected into the peritoneal cavity of BALB/c nude mice. Mice were carefully monitored until they were killed at 4 weeks, at which point peritoneal metastases were examined and recorded.
Caspase-3 (CASP3)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [3]
Response Summary Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 (CASP3) in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors p70S6K and Cyclin D1.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Down regulation
Pathway Response Apoptosis hsa04210
PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
Caveolin-1 (CAV1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [5]
Response Summary This study demonstrated that the key demethylase of m6A FTO promoted the proliferation and metastasis of gastric cancer via regulating the mitochondrial fission/fusion and metabolism. In terms of mechanism, FTO improved the degradation of Caveolin-1 (CAV1) mRNA via its demethylation
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Down regulation
In-vitro Model SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model For the tumor growth analysis, AGS cells were subcutaneously injected into nude mice, and then the tumor volumes were monitored every 5 days. Tumor volumes were estimated based on the length and width and calculated using the following formula: tumor volume = (length × width2)/2. About 1 month later, the nude mice were sacrificed, and then tumors were excised, pictured, and weighed. For the tumor metastasis analysis, AGS cells were injected into nude mice by Tail Vein. About 1 month later, the nude mice were sacrificed, and then lung with metastasis lesions were excised, pictured, and counted.
Cystathionine beta-synthase (CBS)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [6]
Response Summary CBSLR interacted with YTHDF2 to form a CBSLR/YTHDF2/CBS signaling axis that decreased the stability of Cystathionine beta-synthase (CBS) mRNA by enhancing the binding of YTHDF2 with the m6A-modified coding sequence (CDS) of CBS mRNA. Reveal a novel mechanism in how HIF1-Alpha/CBSLR modulates ferroptosis/chemoresistance in GC, illuminating potential therapeutic targets for refractory hypoxic tumors.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
Target Regulation Down regulation
Pathway Response Ubiquitin mediated proteolysis hsa04120
Cell Process Proteasome pathway degradation
In-vitro Model SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
MKN28 Gastric tubular adenocarcinoma Homo sapiens CVCL_1416
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
GSE-1 (Gse-1 is a human gastric epithelial cell line)
BGC-823 Gastric carcinoma Homo sapiens CVCL_3360
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
DNA damage-inducible transcript 3 protein (DDIT3/CHOP)
In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [7]
Response Summary Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of mTORC1 signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DNA damage-inducible transcript 3 protein (DDIT3), which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Responsed Drug Cisplatin Approved
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Down regulation
Pathway Response mTOR signaling pathway hsa04150
Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [7]
Response Summary Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of mTORC1 signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DNA damage-inducible transcript 3 protein (DDIT3), which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Responsed Drug Fluorouracil Approved
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Down regulation
Pathway Response mTOR signaling pathway hsa04150
Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene [7]
Response Summary Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of mTORC1 signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DNA damage-inducible transcript 3 protein (DDIT3), which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Responsed Drug Paclitaxel Approved
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Down regulation
Pathway Response mTOR signaling pathway hsa04150
Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
DNA replication licensing factor MCM5 (MCM5)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [8]
Response Summary In gastric cancer, several component molecules (e.g., DNA replication licensing factor MCM5 (MCM5), MCM6, etc.) of MYC target genes were mediated by METTL3 via altered m6A modification.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model GES-1 Normal Homo sapiens CVCL_EQ22
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
MKN74 Gastric tubular adenocarcinoma Homo sapiens CVCL_2791
pGCC (Primary GC cells)
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
In-vivo Model A total of 2 × 106 GC cells were injected into the flank of nude mice in a 1:1 suspension of BD Matrigel (BD Biosciences) in phosphate-buffered saline (PBS) solution.
DNA replication licensing factor MCM6 (MCM6)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [8]
Response Summary In gastric cancer, several component molecules (e.g., MCM5, DNA replication licensing factor MCM6 (MCM6), etc.) of MYC target genes were mediated by METTL3 via altered m6A modification.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model GES-1 Normal Homo sapiens CVCL_EQ22
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
MKN74 Gastric tubular adenocarcinoma Homo sapiens CVCL_2791
pGCC (Primary GC cells)
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
In-vivo Model A total of 2 × 106 GC cells were injected into the flank of nude mice in a 1:1 suspension of BD Matrigel (BD Biosciences) in phosphate-buffered saline (PBS) solution.
Frizzled-7 (FZD7)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [9]
Response Summary Mutated YTHDF1 enhanced expression of Frizzled-7 (FZD7), leading to hyperactivation of the Wnt/Bete-catenin pathway and promotion of gastric cancer carcinogenesis.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
Target Regulation Up regulation
Pathway Response Wnt signaling pathway hsa04310
In-vitro Model MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
In-vivo Model Stable short hairpin (shRNA)-expressing MGC-803 cells (3 × 106) were suspended in 0.1 mL PBS and injected into the flanks of BALB/c mice (n = 8 mice/group) at 5-6 weeks of age. For the flanks injected mice, tumor growth was examined every 3 days. After 5 weeks, mice were sacrificed by cervical dislocation, and weight of xenografts was tested.BALB/c mice were randomly divided into three groups (n = 4 mice/group). A total of 3 × 106 stable shRNA-expressing MGC-803 cells were resuspended in 0.1 mL PBS and injected into the abdominal cavity. After 4 weeks, mice were sacrificed by cervical dislocation, abdominal cavities were opened, and the numbers of implantation metastasis were counted.For the pulmonary metastasis model, NOD/SCID mice were randomly divided into three groups (n = 4 mice/group). A total of 1 × 105 stable shRNA-expressing MGC-803 cells were resuspended in 0.1 mL PBS and injected into the lateral tail vein. After 7 weeks, mice were sacrificed by cervical dislocation, and lungs were extracted and fixed 4% paraformaldehyde in PBS. Paraffin embedding, sectioning, and staining with hematoxylin and eosin were performed. Visible lung metastases were measured and counted using a microscope.
G1/S-specific cyclin-D1 (CCND1)
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [3]
Response Summary Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors p70S6K and G1/S-specific cyclin-D1 (CCND1).
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [10]
Response Summary METTL16-mediated m6A methylation promotes proliferation of gastric cancer cells through enhancing G1/S-specific cyclin-D1 (CCND1) expression.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 16 (METTL16) WRITER
Target Regulation Up regulation
Pathway Response Cell cycle hsa04110
Cell Process G1/S blocking
In-vitro Model SNU-719 Gastric tubular adenocarcinoma Homo sapiens CVCL_5086
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
MKN28 Gastric tubular adenocarcinoma Homo sapiens CVCL_1416
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
GES-1 Normal Homo sapiens CVCL_EQ22
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model Xenograft mouse model was used to verify the tumorigenic effect of METTL16 in vivo. BALB/c nude mice (4 weeks old) were injected with METTL16 gene knock-down stable MGC803 GC cells (3 × 106 cells/mice, subcutaneous injection) or shNC control cells (3 × 106, subcutaneous injection), and the dose was 100 uL, with PBS as solvent. The tumour size was measured every 3-5 days. At the end of feeding (6 weeks after subcutaneous injection), the mice were killed and the tumours were extracted for histological analysis.
Hepatoma-derived growth factor (HDGF)
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [11]
Response Summary Elevated METTL3 expression promotes tumour angiogenesis and glycolysis in Gastric cancer. P300-mediated H3K27 acetylation activation in the promoter of METTL3 induced METTL3 transcription, which stimulated m6A modification of Hepatoma-derived growth factor (HDGF) mRNA, and the m6A reader IGF2BP3 then directly recognised and bound to the m6A site on HDGF mRNA and enhanced HDGF mRNA stability.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response Glycolysis / Gluconeogenesis hsa00010
Cell Process Glycolysis
In-vitro Model HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
NCI-N87 Gastric tubular adenocarcinoma Homo sapiens CVCL_1603
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
In-vivo Model Mice 8 weeks after splenic portal vein injection of BGC823 cells with METTL3 overexpression or vector-transfected cells.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [11]
Response Summary Elevated METTL3 expression promotes tumour angiogenesis and glycolysis in Gastric cancer. P300-mediated H3K27 acetylation activation in the promoter of METTL3 induced METTL3 transcription, which stimulated m6A modification of Hepatoma-derived growth factor (HDGF) mRNA, and the m6A reader IGF2BP3 then directly recognised and bound to the m6A site on HDGF mRNA and enhanced HDGF mRNA stability.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) READER
Target Regulation Up regulation
Pathway Response Glycolysis / Gluconeogenesis hsa00010
Cell Process Glycolysis
In-vitro Model HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
NCI-N87 Gastric tubular adenocarcinoma Homo sapiens CVCL_1603
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
In-vivo Model Mice 8 weeks after splenic portal vein injection of BGC823 cells with METTL3 overexpression or vector-transfected cells.
Hexokinase-2 (HK2)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [12]
Response Summary Oncogenic role of WTAP and its m6A-mediated regulation on gastric cancer Warburg effect, providing a novel approach and therapeutic target in gastric cancer. WTAP enhanced the stability of Hexokinase-2 (HK2) mRNA through binding with the 3'-UTR m6A site.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Wilms tumor 1-associating protein (WTAP) WRITER
Target Regulation Up regulation
Pathway Response Glycolysis / Gluconeogenesis hsa00010
Cell Process Glycolysis
In-vitro Model SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
GES-1 Normal Homo sapiens CVCL_EQ22
BGC-823 Gastric carcinoma Homo sapiens CVCL_3360
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
Homeobox protein Hox-B13 (HOXB13)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [13]
Response Summary FTO suppresses Homeobox protein Hox-B13 (HOXB13) methytlation; FTO and HOXB13 expression promotes GC cell proliferation, migration, and invasion. HOXB13 expression intensifies GC invasion through PI3K/AKT/mTOR signaling via IGF-1R.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Down regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
mTOR signaling pathway hsa04150
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model SNU-5 Gastric adenocarcinoma Homo sapiens CVCL_0078
NCI-N87 Gastric tubular adenocarcinoma Homo sapiens CVCL_1603
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
GES-1 Normal Homo sapiens CVCL_EQ22
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model Male nu/nu mice between 4 and 6 weeks of age received subcutaneous injections of equivalent AGS cells expressing either control or LV-HOXB13 within 30 min of harvesting on the right and left flanks.
Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [14]
Response Summary IGF2BP3 positively regulated Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A) expression by directly binding to a specific m6A site in the coding region of HIF1A mRNA in gastric cancer cells. IGF2BP3 and HIF1A were highly expressed in GC tissues and hypoxia-treated GC cells.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) READER
Target Regulation Up regulation
Cell Process Cell migration
In-vitro Model MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
HUVEC-C Normal Homo sapiens CVCL_2959
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
Insulin-like growth factor 1 receptor (IGF1R)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [15]
Response Summary IGF2BP2, as a m6A reader, was proved to increase the expression of Insulin-like growth factor 1 receptor (IGF1R) by identifying m6A methylation modification sites in IGF1R mRNA, thus activating RhoA-ROCK pathway. The oncogenic role of IGF2BP2 in gastric cancer carcinogenesis and confirmed its activation is partly due to the activation of IGF1R-RhoA-ROCK signaling pathway.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) READER
Target Regulation Up regulation
In-vitro Model SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
MKN1 Gastric adenosquamous carcinoma Homo sapiens CVCL_1415
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
GES-1 Normal Homo sapiens CVCL_EQ22
In-vivo Model A total of 30 BALB/c nude mice were chosen and assigned to three groups: (1) control (injected with 0.2 mL PBS), (2) si-NC (injected with si-NC transfected SGC7901 cells) and (3) si-IGF2BP2 (injected with si-IGF2BP2 transfected SGC7901 cells (n = 5 per group). 2 × 106 SGC7901 cells were injected into the left right back of each mouse through subcutaneous injection. Tumor sizes were recorded once per week. After 28 days, the mice were euthanized, and tumor tissues were weighted.
Integrin beta-1 (ITGB1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [16]
Response Summary FTO was an independent risk factor for overall survival (OS) of GC patients and FTO could promote GC metastasis by upregulating the expression of Integrin beta-1 (ITGB1) via decreasing its m6A level.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Up regulation
In-vitro Model SNU-216 Gastric tubular adenocarcinoma Homo sapiens CVCL_3946
MKN7 Gastric tubular adenocarcinoma Homo sapiens CVCL_1417
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
BGC-823 Gastric carcinoma Homo sapiens CVCL_3360
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
Interferon gamma receptor 1 (IFNGR1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [17]
Response Summary Loss of YTHDF1 mediated the overexpression of Interferon gamma receptor 1 (IFNGR1) and JAK/STAT1 signaling pathway in tumor cells, which contributes to restored sensitivity to antitumor immunity. YTHDF1 is overexpressed in GC and promotes GC by inducing cell proliferation and repression of DCs-mediated antitumor immune response.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
Target Regulation Down regulation
Pathway Response JAK-STAT signaling pathway hsa04630
Cell Process Immunity
In-vitro Model YTN16 (Mouse gastric cancer cell line (YTN16))
MKN74 Gastric tubular adenocarcinoma Homo sapiens CVCL_2791
BGC-823 Gastric carcinoma Homo sapiens CVCL_3360
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model MKN74 cells (5×106/tumor) expressing shNC, shYTHDF1-1, or shYTHDF1-2 were suspended in ice-cold 100 ul PBS:Matrigel gel (1:1, v/v) (Corning, USA), and subcutaneously implanted into the right dorsal flank of 4-week-old NOD.
Krueppel-like factor 2 (KLF2)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [18]
Response Summary METTL3 promotes translation of SPHK2 mRNA via an m6A-YTHDF1-dependent manner. Functionally, SPHK2 facilitates GC cell proliferation, migration and invasion by inhibiting Krueppel-like factor 2 (KLF2) expression.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Down regulation
Cell Process Cell proliferation
Cell migration
Cell invasion
Mammalian target of rapamycin complex 1 (mTORC1)
In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [7]
Response Summary Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of Mammalian target of rapamycin complex 1 (mTORC1) signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DDIT3, which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Responsed Drug Cisplatin Approved
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Down regulation
Pathway Response mTOR signaling pathway hsa04150
Cell Process Cell apoptosis
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [7]
Response Summary Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of Mammalian target of rapamycin complex 1 (mTORC1) signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DDIT3, which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Responsed Drug Fluorouracil Approved
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Down regulation
Pathway Response mTOR signaling pathway hsa04150
Cell Process Cell apoptosis
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene [7]
Response Summary Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of Mammalian target of rapamycin complex 1 (mTORC1) signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DDIT3, which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Responsed Drug Paclitaxel Approved
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Down regulation
Pathway Response mTOR signaling pathway hsa04150
Cell Process Cell apoptosis
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
Mutated in multiple advanced cancers 1 (PTEN)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [19]
Response Summary METTL14 inhibits tumor growth and metastasis of Stomach Adenocarcinoma via stabilization of Mutated in multiple advanced cancers 1 (PTEN) mRNA expression. Therefore, METTL14 is a potential biomarker of prognosis and therapeutic targets for Stomach Adenocarcinoma.
Responsed Disease Gastric cancer [ICD-11: 2B72.Z]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Up regulation
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model RGM1 Normal Rattus norvegicus CVCL_0499
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
BGC-823 Gastric carcinoma Homo sapiens CVCL_3360
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model For the purpose of enhancing the overall randomization of the experiment, a random comparison table had been employed. Accordingly, 5-wk-old male nude athymic BALB/c nu/nu mice (Slack, Shanghai, China) were randomly divided into two parts including a control group (NC) and the experimental group METTL14-OE. For developing subcutaneous xeno transplantation model, 5 × 106 HGC-27 cells stably transfected with NC or METTL14 overexpression were subcutaneously incorporated for 5-week-old BALB/c nude mice. The mice experienced euthanasia after 27 days of inoculation and obtained xenografts's mass was obtained. Tumor volume over three days was obtained. To create mouse STAD liver metastasis orthotopic tumor model, 1 × 106 HGC-27 cells under stable transfection with NC or METTL14 overexpression were added to subserosal gastric wall of BALB/c nude mice.
Myc proto-oncogene protein (MYC)
In total 4 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [8]
Response Summary In gastric cancer, several component molecules (e.g., MCM5, MCM6, etc.) of Myc proto-oncogene protein (MYC) target genes were mediated by METTL3 via altered m6A modification.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model GES-1 Normal Homo sapiens CVCL_EQ22
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
MKN74 Gastric tubular adenocarcinoma Homo sapiens CVCL_2791
pGCC (Primary GC cells)
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
In-vivo Model A total of 2 × 106 GC cells were injected into the flank of nude mice in a 1:1 suspension of BD Matrigel (BD Biosciences) in phosphate-buffered saline (PBS) solution.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [20]
Response Summary METTL3 enhanced Myc proto-oncogene protein (MYC) m6A methylation and increased MYC translation, which could potentiate the proliferation, migration and invasion of gastric cancer cells.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Cell Process Cell proliferation
Cell migration
Cell invasion
Cell apoptosis
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
AZ-521 Duodenal adenocarcinoma Homo sapiens CVCL_2862
GES-1 Normal Homo sapiens CVCL_EQ22
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
In-vivo Model The GC cell line MKN-45 stably infected with lentivirus expressing sh-HBXIP was prepared into 5 × 107 cells/mL cell suspension.
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene [21]
Response Summary IGF2BP1 upregulated in GC tissue and acted as a predictor of poor prognosis for GC patients. IGF2BP1 directly interacted with Myc proto-oncogene protein (MYC) mRNA via m6A-dependent manner to by stabilize its stability.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) READER
Target Regulation Up regulation
Pathway Response Central carbon metabolism in cancer hsa05230
Glycolysis / Gluconeogenesis hsa00010
Cell Process Aerobic glycolysis
In-vitro Model SNU-216 Gastric tubular adenocarcinoma Homo sapiens CVCL_3946
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
GES-1 Normal Homo sapiens CVCL_EQ22
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model A total of 5 × 106 transfected MKN-45 cells, stably transfected with sh-IGF2BP1 vector or empty vector were subcutaneously injected into the flank of the mice. Tumor growth was measured every three days, and calculated using the following equation = a × b2/2 (a for longitudinal diameter; and b for latitudinal diameter). Three weeks after injection, mice were sacrificed.
Experiment 4 Reporting the m6A-centered Disease Response by This Target Gene [20]
Response Summary Expressions of HBXIP, METTL3 and Myc proto-oncogene protein (MYC) were all determined to be upregulated in both GC tissues and cells. HBXIP plays an oncogenic role in GC via METTL3-mediated MYC mRNA m6A modification.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Cell Process Cell proliferation
Cell migration
Cell invasion
Cell apoptosis
In-vitro Model SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
GES-1 Normal Homo sapiens CVCL_EQ22
AZ-521 Duodenal adenocarcinoma Homo sapiens CVCL_2862
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model The GC cell line MKN-45 stably infected with lentivirus expressing sh-HBXIP was prepared into 5 × 107 cells/mL cell suspension. The cell suspension was injected into the left axilla of nude mice using a 1 mL syringe as the sh-HBXIP group (n = 6). The GC cell line MKN-45 infected with the lentivirus expressing sh-NC was dispersed into the cell suspension, which was injected into nude mice as the sh-NC group (n = 6). Tumor growth was observed and data were recorded after inoculation. On the 26th day, all nude mice were euthanized by cervical dislocation and the tumors were resected and weighed.
Myt1 kinase (PKMYT1)
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [22]
Response Summary Myt1 kinase (PKMYT1), as a downstream target of ALKBH5, promoted invasion and migration in GC. Moreover IGF2BP3 helped stabilize the mRNA stability of PKMYT1 via its m6A modification site.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
Target Regulation Down regulation
Cell Process Cell invasion
Cell migration
In-vitro Model SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
BGC-823 Gastric carcinoma Homo sapiens CVCL_3360
In-vivo Model After randomly assignment and anesthetization, nude mice were injected with 5 × 106 cells suspended in 100 uL PBS into the tail vein (n = 5 per group).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [22]
Response Summary Myt1 kinase (PKMYT1), as a downstream target of ALKBH5, promoted invasion and migration in GC. Moreover IGF2BP3 helped stabilize the mRNA stability of PKMYT1 via its m6A modification site.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) READER
Target Regulation Up regulation
Cell Process Cell invasion
Cell migration
In-vitro Model SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
BGC-823 Gastric carcinoma Homo sapiens CVCL_3360
In-vivo Model After randomly assignment and anesthetization, nude mice were injected with 5 × 106 cells suspended in 100 uL PBS into the tail vein (n = 5 per group).
NAD-dependent protein deacetylase sirtuin-1 (SIRT1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [23]
Response Summary IGF2BP2 regulated GC the proliferation/migration through recognizing the m6A modification sites of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) mRNA.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) READER
Cell Process Cell proliferation
Cell migration
In-vitro Model SNU-216 Gastric tubular adenocarcinoma Homo sapiens CVCL_3946
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
GES-1 Normal Homo sapiens CVCL_EQ22
In-vivo Model About 5 × 106 MKN45 cells stably transfected with IGF2BP2 shRNA or sh-NC vectors were subcutaneously injected into flank of nude mice.
PI3-kinase subunit alpha (PI3k/PIK3CA)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [24]
Response Summary The m6A modification level was decreased in GC and METTL14 was a key regulator resulting in m6A disorder in GC. METTL14 overexpression suppressed GC cell proliferation and aggression by deactivating the PI3-kinase subunit alpha (PI3k/PIK3CA)/AKT/mTOR pathway and the EMT pathway, respectively.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Down regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
mTOR signaling pathway hsa04150
In-vitro Model SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
GES-1 Normal Homo sapiens CVCL_EQ22
Poly [ADP-ribose] polymerase 1 (PARP1)
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [25]
Response Summary m6A methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+ gastric cancer stem cells by Promoting Poly [ADP-ribose] polymerase 1 (PARP1) mRNA stability which increases base excision repair pathway activity. METTTL3 enhances the stability of PARP1 by recruiting YTHDF1 to target the 3'-untranslated Region (3'-UTR) of PARP1 mRNA.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Responsed Drug Oxaliplatin Approved
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response Nucleotide excision repair hsa03420
Signaling pathways regulating pluripotency of stem cells hsa04550
Cell Process RNA stability
Excision repair
In-vitro Model SNU-719 Gastric tubular adenocarcinoma Homo sapiens CVCL_5086
MKN74 Gastric tubular adenocarcinoma Homo sapiens CVCL_2791
HEK293T Normal Homo sapiens CVCL_0063
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model 100,000 pLKO and PARP1-sh1 (PT1 and PT2) cells were mixed with matrix gel and inoculate into BALB/C nude mice, respectively. After 25 days, 6 organoid transplanted tumor mice were treated with oxaliplatin (Sellekchem, s1224) twice a week for 4 weeks at a dose of 5 mg/kg.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [25]
Response Summary m6A methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+ gastric cancer stem cells by Promoting PARP1 mRNA stability which increases base excision repair pathway activity. METTTL3 enhances the stability of PARP1 by recruiting Poly [ADP-ribose] polymerase 1 (PARP1) to target the 3'-untranslated Region (3'-UTR) of PARP1 mRNA.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Responsed Drug Oxaliplatin Approved
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
Target Regulation Up regulation
Pathway Response Nucleotide excision repair hsa03420
Signaling pathways regulating pluripotency of stem cells hsa04550
Cell Process RNA stability
Excision repair
In-vitro Model SNU-719 Gastric tubular adenocarcinoma Homo sapiens CVCL_5086
MKN74 Gastric tubular adenocarcinoma Homo sapiens CVCL_2791
HEK293T Normal Homo sapiens CVCL_0063
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model 100,000 pLKO and PARP1-sh1 (PT1 and PT2) cells were mixed with matrix gel and inoculate into BALB/C nude mice, respectively. After 25 days, 6 organoid transplanted tumor mice were treated with oxaliplatin (Sellekchem, s1224) twice a week for 4 weeks at a dose of 5 mg/kg.
Proline-rich AKT1 substrate 1 (AKT1S1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [26]
Response Summary METTL14-mediated m6A modification of circORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p/Proline-rich AKT1 substrate 1 (AKT1S1) axis. METTL14 was downregulated in GC tissue samples and its low expression acted as a prognostic factor of poor survival in patients with GC.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Down regulation
In-vitro Model SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
MKN28 Gastric tubular adenocarcinoma Homo sapiens CVCL_1416
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
GES-1 Normal Homo sapiens CVCL_EQ22
BGC-823 Gastric carcinoma Homo sapiens CVCL_3360
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
RAC-alpha serine/threonine-protein kinase (AKT1)
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [3]
Response Summary Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of RAC-alpha serine/threonine-protein kinase (AKT1) and expression of down-stream effectors p70S6K and Cyclin D1.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response Apoptosis hsa04210
PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [24]
Response Summary The m6A modification level was decreased in GC and METTL14 was a key regulator resulting in m6A disorder in GC. METTL14 overexpression suppressed GC cell proliferation and aggression by deactivating the PI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR pathway and the EMT pathway, respectively.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Down regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
mTOR signaling pathway hsa04150
In-vitro Model SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
GES-1 Normal Homo sapiens CVCL_EQ22
Rho GTPase activating protein 5 (ARHGAP5)
In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [27]
Response Summary ARHGAP5-AS1 also stabilized ARHGAP5 mRNA in the cytoplasm by recruiting METTL3 to stimulate m6A modification of Rho GTPase activating protein 5 (ARHGAP5) mRNA. As a result, ARHGAP5 was upregulated to promote chemoresistance and its upregulation was also associated with poor prognosis in gastric cancer. downregulation of ARHGAP5-AS1 in resistant cells evidently reversed the resistance to chemotherapeutic drugs including cisplatin (DDP), ADM, and 5-FU.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Responsed Drug Cisplatin Approved
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response Autophagy hsa04140
Cell Process Cellular Processes
Transport and catabolism
In-vitro Model BGC-823 Gastric carcinoma Homo sapiens CVCL_3360
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [27]
Response Summary ARHGAP5-AS1 also stabilized ARHGAP5 mRNA in the cytoplasm by recruiting METTL3 to stimulate m6A modification of Rho GTPase activating protein 5 (ARHGAP5) mRNA. As a result, ARHGAP5 was upregulated to promote chemoresistance and its upregulation was also associated with poor prognosis in gastric cancer. downregulation of ARHGAP5-AS1 in resistant cells evidently reversed the resistance to chemotherapeutic drugs including cisplatin (DDP), ADM, and 5-FU.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Responsed Drug Fluorouracil Approved
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response Autophagy hsa04140
Cell Process Cellular processes
Cellular transport, Cellular catabolism
In-vitro Model BGC-823 Gastric carcinoma Homo sapiens CVCL_3360
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene [27]
Response Summary ARHGAP5-AS1 also stabilized ARHGAP5 mRNA in the cytoplasm by recruiting METTL3 to stimulate m6A modification of Rho GTPase activating protein 5 (ARHGAP5) mRNA. As a result, ARHGAP5 was upregulated to promote chemoresistance and its upregulation was also associated with poor prognosis in gastric cancer. downregulation of ARHGAP5-AS1 in resistant cells evidently reversed the resistance to chemotherapeutic drugs including cisplatin (DDP), ADM, and 5-FU.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Responsed Drug Adriamycin Phase 3
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response Autophagy hsa04140
Cell Process Cellular processes
Cellular transport, Cellular catabolism
In-vitro Model BGC-823 Gastric carcinoma Homo sapiens CVCL_3360
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
Ribosomal protein S6 kinase beta-1 (RPS6KB1/p70S6K)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [3]
Response Summary Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors Ribosomal protein S6 kinase beta-1 (RPS6KB1/p70S6K) and Cyclin D1.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
Serine/threonine-protein kinase mTOR (MTOR)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [24]
Response Summary The m6A modification level was decreased in GC and METTL14 was a key regulator resulting in m6A disorder in GC. METTL14 overexpression suppressed GC cell proliferation and aggression by deactivating the PI3K/AKT/Serine/threonine-protein kinase mTOR (MTOR) pathway and the EMT pathway, respectively.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Down regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
mTOR signaling pathway hsa04150
In-vitro Model SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
GES-1 Normal Homo sapiens CVCL_EQ22
Serine/threonine-protein kinase ULK1 (ULK1/ATG1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [28]
Response Summary Knockdown of FTO reversed cisplatin resistance of SGC-7901/DDP cells both in vitro and in vivo, which was attributed to the inhibition of Serine/threonine-protein kinase ULK1 (ULK1)-mediated autophagy. These findings indicate that the FTO/ULK1 axis exerts crucial roles in cisplatin resistance of gastric cancer.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Responsed Drug Cisplatin Approved
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Up regulation
In-vitro Model GES-1 Normal Homo sapiens CVCL_EQ22
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
In-vivo Model A total of 5 × 106 cells in 200 ul PBS were injected subcutaneously into the flanks of nude mice. After injection, cisplatin treatment was initiated on day 5. Mice were injected with 5 mg/kg cisplatin or PBS solution in the abdominal cavity once a week for 3?weeks.
Sphingosine kinase 2 (SPHK2)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [18]
Response Summary METTL3 promotes translation of Sphingosine kinase 2 (SPHK2) mRNA via an m6A-YTHDF1-dependent manner. Functionally, SPHK2 facilitates GC cell proliferation, migration and invasion by inhibiting KLF2 expression.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Cell Process Cell proliferation
Cell migration
Cell invasion
Suppressor of cytokine signaling 2 (SOCS2)
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-KO in gastric cancer cells resulted in the suppression of cell proliferation by inducing Suppressor of cytokine signaling 2 (SOCS2), suggesting a potential role of elevated METTL3 expression in gastric cancer progression.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Down regulation
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
Transcription factor E2F3 (E2F3)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [30]
Response Summary Reveal the compelling role of m6A in GC and highlight the regulatory function of the miR-660/Transcription factor E2F3 (E2F3) pathway in Gastric cancer progression.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Pathway Response MicroRNAs in cancer hsa05206
Cell Process Cell proliferation
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
GES-1 Normal Homo sapiens CVCL_EQ22
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
MKN28 Gastric tubular adenocarcinoma Homo sapiens CVCL_1416
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
Transcription factor Jun (c-Jun/JUN)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [31]
Response Summary KIAA1429 played a key role in promoting gastric cancer by regulating Transcription factor Jun (c-Jun/JUN) expression in an m6A independent manner.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Protein virilizer homolog (VIRMA) WRITER
Target Regulation Up regulation
Pathway Response Cell cycle hsa04110
Cell Process Arrest cell cycle at the S phase
In-vitro Model MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
In-vivo Model Gastric cancer cell line MGC803 (shRNA-NC or shKIAA1429; 1 × 107) was injected subcutaneously into the armpit of BALB/c nude mice (5-week-old, male, n = 4 for each group). Tumor growth was monitored at 3-day intervals.
Transcriptional coactivator YAP1 (YAP1)
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [32]
Response Summary High YTHDC2 was strongly positively correlated with high Transcriptional coactivator YAP1 (YAP1) in clinical GC tissues, YTHDC2 is a novel oncogene in GC, which provides the theoretical basis for the strategy of targeting YTHDC2 for GC patients.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator YTH domain-containing protein 2 (YTHDC2) READER
Target Regulation Up regulation
In-vitro Model HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model They were subcutaneously and caudal vein injected with YTHDC2 knockout AGS cells, respectively. After 7 weeks, the mice were sacrificed and tumor size and lung metastasis nodules were recorded.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [33]
Response Summary The expression of m6A and METTL3 was upregulated in human gastric cancer tissues and gastric cancer cell lines. m6A methyltransferase METTL3 promoted the proliferation and migration of gastric cancer cells through the m6A modification of Transcriptional coactivator YAP1 (YAP1).
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Cell Process Cell proliferation
Cell metastasis
In-vitro Model MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
GES-1 Normal Homo sapiens CVCL_EQ22
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
Translocation protein SEC62 (SEC62)
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [34]
Response Summary miR-4429 prevented gastric cancer progression through targeting METTL3 to inhibit m6A-caused stabilization of Translocation protein SEC62 (SEC62), indicating miR-4429 as a promising target for treatment improvement for Gastric cancer. METTL3 interacted with SEC62 to induce the m6A on SEC62 mRNA, therefore facilitated the stabilizing effect of IGF2BP1 on SEC62 mRNA.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response Protein processing in endoplasmic reticulum hsa04141
Cell Process RNA stability
Cell apoptosis
In-vitro Model GES-1 Normal Homo sapiens CVCL_EQ22
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [34]
Response Summary miR-4429 prevented gastric cancer progression through targeting METTL3 to inhibit m6A-caused stabilization of Translocation protein SEC62 (SEC62), indicating miR-4429 as a promising target for treatment improvement for Gastric cancer. METTL3 interacted with SEC62 to induce the m6A on SEC62 mRNA, therefore facilitated the stabilizing effect of IGF2BP1 on SEC62 mRNA.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) READER
Target Regulation Up regulation
Pathway Response Protein processing in endoplasmic reticulum hsa04141
Cell Process RNA stability
Cell apoptosis
In-vitro Model GES-1 Normal Homo sapiens CVCL_EQ22
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
Ubiquitin carboxyl-terminal hydrolase 14 (USP14)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [35]
Response Summary YTHDF1 promoted Ubiquitin carboxyl-terminal hydrolase 14 (USP14) protein translation in an m6A-dependent manner. USP14 upregulation was positively correlated with YTHDF1 expression and indicated a poor prognosis in gastric cancer.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
Target Regulation Up regulation
Cell Process Cell proliferation and invasion
Cell apoptosis
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
BGC-823 Gastric carcinoma Homo sapiens CVCL_3360
GES-1 Normal Homo sapiens CVCL_EQ22
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
MKN28 Gastric tubular adenocarcinoma Homo sapiens CVCL_1416
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
In-vivo Model BGC-823 cells (5 × 106) with shRNAs targeting YTHDF1 (sh-YTHDF1) or shRNAs targeting control (sh-NC) were trypsinized and suspended in 0.1 mL PBS and injected subcutaneously into the BALB/c mice (n = 5 mice per group).
Zinc finger MYM-type protein 1 (ZMYM1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [36]
Response Summary The m6A modification of Zinc finger MYM-type protein 1 (ZMYM1) mRNA by METTL3 enhanced its stability relying on the "reader" protein HuR (also known as ELAVL1) dependent pathway.The study uncover METTL3/ZMYM1/E-cadherin signaling as a potential therapeutic target in anti-metastatic strategy against Gastric cancer.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response Cytokine-cytokine receptor interaction hsa04060
Cell Process Epithelial-mesenchymal transition
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
BGC-823 Gastric carcinoma Homo sapiens CVCL_3360
GES-1 Normal Homo sapiens CVCL_EQ22
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
MKN28 Gastric tubular adenocarcinoma Homo sapiens CVCL_1416
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
In-vivo Model The luciferase signal intensity from days 7 to 42 is on equivalent scales in the models. Bioluminescent flux (photons/s/cm2/steradian) was determined for the lung metastases.
ACBD3 antisense RNA 1 (ACBD3-AS1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [37]
Response Summary m6A lncRNA is closely related to the occurrence and progression of gastric cancer. ACBD3 antisense RNA 1 (ACBD3-AS1) was overexpressed in tumor tissue. Naive B cell, Plasma cells, resting CD4 memory T cell were highly infiltrated tissues in cluster 2, while Macrophages M2, resting Mast cells, Monocytes, regulates T cells were lowly in cluster 1.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Pathway Response T cell receptor signaling pathway hsa04660
Cell Process Immune
Long intergenic non-protein coding RNA 1320 (LINC01320)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [38]
Response Summary In gastric cancer, METTL14 was involved in the m6A modification of LINC01320 and induced the up-regulation of Long intergenic non-protein coding RNA 1320 (LINC01320).
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Up regulation
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
GES-1 Normal Homo sapiens CVCL_EQ22
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
MKN7 Gastric tubular adenocarcinoma Homo sapiens CVCL_1417
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
NCI-N87 Gastric tubular adenocarcinoma Homo sapiens CVCL_1603
Long intergenic non-protein coding RNA 470 (LINC00470)
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [39]
Response Summary Long intergenic non-protein coding RNA 470 (LINC00470)-METTL3-mediated PTEN mRNA degradation relied on the m6A reader protein YTHDF2-dependent pathway. LINC00470 served as a therapeutic target for Gastric cancer patients.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
Target Regulation Up regulation
Pathway Response Gastric cancer hsa05226
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
BGC-823 Gastric carcinoma Homo sapiens CVCL_3360
GES-1 Normal Homo sapiens CVCL_EQ22
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [39]
Response Summary Long intergenic non-protein coding RNA 470 (LINC00470)-METTL3-mediated PTEN mRNA degradation relied on the m6A reader protein YTHDF2-dependent pathway.LINC00470 served as a therapeutic target for Gastric cancer patients.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response Gastric cancer hsa05226
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
BGC-823 Gastric carcinoma Homo sapiens CVCL_3360
GES-1 Normal Homo sapiens CVCL_EQ22
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
Long intergenic non-protein coding RNA 958 (LINC00958)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [40]
Response Summary Long intergenic non-protein coding RNA 958 (LINC00958) accelerated the aerobic glycolysis of GC cells. Mechanistically, KIAA1429 interacted with the m6A modification site and promoted the enrichment of LINC00958, and LINC00958 subsequently cooperated with GLUT1 mRNA to enhance its mRNA stability.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Protein virilizer homolog (VIRMA) WRITER
Target Regulation Up regulation
Cell Process Glycolysis
In-vitro Model SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
GES-1 Normal Homo sapiens CVCL_EQ22
BGC-823 Gastric carcinoma Homo sapiens CVCL_3360
In-vivo Model Ten four-week-old BALB/c nude mice were injected with LINC00958-overexpressing or vector-transfected cells. Briefly, 5 × 106 cells were subcutaneously injected in the flank of mice. Four weeks after injection, the mice were sacrificed and examined by weighting.
Nuclear paraspeckle assembly transcript 1 (NEAT1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [41]
Response Summary ALKBH5 promotes Gastric cancer invasion and metastasis by demethylating the lncRNA Nuclear paraspeckle assembly transcript 1 (NEAT1).
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
Target Regulation Up regulation
Cell Process Cell proliferation and metastasis
In-vitro Model BGC-823 Gastric carcinoma Homo sapiens CVCL_3360
GES-1 Normal Homo sapiens CVCL_EQ22
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
THAP7 antisense RNA 1 (THAP7-AS1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [42]
Response Summary LV-sh-THAP7 antisense RNA 1 (THAP7-AS1) treatment could suppress gastric cancer growth. THAP7-AS1, transcriptionally activated by SP1 and then modified by METTL3-mediated m6A, exerts oncogenic functions, by promoting interaction between NLS and importin alpha-1 and then improving the CUL4B protein entry into the nucleus to repress the transcription of miR-22-3p and miR-320a.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Cell growth
Cell invasion
Cell metastasis
microRNA 660 (MIR660)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [30]
Response Summary Reveal the compelling role of m6A in GC and highlight the regulatory function of the microRNA 660 (MIR660)/E2F3 pathway in Gastric cancer progression.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Pathway Response MicroRNAs in cancer hsa05206
Cell Process Cell proliferation
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
GES-1 Normal Homo sapiens CVCL_EQ22
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
MKN28 Gastric tubular adenocarcinoma Homo sapiens CVCL_1416
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
hsa-miR-30c-2-3p
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [26]
Response Summary METTL14-mediated m6A modification of circORC5 suppresses gastric cancer progression by regulating hsa-miR-30c-2-3p/AKT1S1 axis.METTL14 was downregulated in GC tissue samples and its low expression acted as a prognostic factor of poor survival in patients with GC.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Up regulation
In-vitro Model SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
MKN28 Gastric tubular adenocarcinoma Homo sapiens CVCL_1416
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
GES-1 Normal Homo sapiens CVCL_EQ22
BGC-823 Gastric carcinoma Homo sapiens CVCL_3360
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
hsa_circ_0066779 (circPVRL3)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [43]
Response Summary Down-regulation of hsa_circ_0066779 (circPVRL3) could promote the proliferation in gastric carcinoma and have potential to encode protein.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Cell Process Encode protein
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [6]
Response Summary CBSLR interacted with YTHDF2 to form a CBSLR/YTHDF2/CBS signaling axis that decreased the stability of CBS mRNA by enhancing the binding of YTHDF2 with the m6A-modified coding sequence (CDS) of CBS mRNA. Reveal a novel mechanism in how HIF1-Alpha/CBSLR modulates ferroptosis/chemoresistance in GC, illuminating potential therapeutic targets for refractory hypoxic tumors.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
Target Regulation Up regulation
Pathway Response Ubiquitin mediated proteolysis hsa04120
Cell Process Proteasome pathway degradation
In-vitro Model SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
MKN28 Gastric tubular adenocarcinoma Homo sapiens CVCL_1416
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
GSE-1 (Gse-1 is a human gastric epithelial cell line)
BGC-823 Gastric carcinoma Homo sapiens CVCL_3360
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
Circ_ORC5
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [26]
Response Summary METTL14-mediated m6A modification of Circ_ORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p/AKT1S1 axis. METTL14 was downregulated in GC tissue samples and its low expression acted as a prognostic factor of poor survival in patients with GC.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Down regulation
In-vitro Model SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
MKN28 Gastric tubular adenocarcinoma Homo sapiens CVCL_1416
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
GES-1 Normal Homo sapiens CVCL_EQ22
BGC-823 Gastric carcinoma Homo sapiens CVCL_3360
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
miR-17-92
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [45]
Response Summary In gastric cancer, m6A facilitated processing of pri-miR-17-92 into the miR-17-92 cluster through an m6A/DGCR8-dependent mechanism. METTL3-high tumors showed preferred sensitivity to an mTOR inhibitor, everolimus.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Responsed Drug Everolimus Approved
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response mTOR signaling pathway hsa04150
PI3K-Akt signaling pathway hsa04151
Cell Process miRNA maturation
In-vitro Model MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model For subcutaneous xenograft models, 0.1 mL of cell suspension containing 106 cells were injected subcutaneously into the right flank of mice (n = 6 for each group).
References
Ref 1 METTL3-Mediated ADAMTS9 Suppression Facilitates Angiogenesis and Carcinogenesis in Gastric Cancer. Front Oncol. 2022 Apr 28;12:861807. doi: 10.3389/fonc.2022.861807. eCollection 2022.
Ref 2 Dysregulated N6-methyladenosine?methylation writer METTL3 contributes to the proliferation and migration of gastric cancer. J Cell Physiol. 2020 Jan;235(1):548-562. doi: 10.1002/jcp.28994. Epub 2019 Jun 24.
Ref 3 METTL3 Promotes the Proliferation and Mobility of Gastric Cancer Cells. Open Med (Wars). 2019 Mar 2;14:25-31. doi: 10.1515/med-2019-0005. eCollection 2019.
Ref 4 m(6)A modification-mediated BATF2 acts as a tumor suppressor in gastric cancer through inhibition of ERK signaling. Mol Cancer. 2020 Jul 10;19(1):114. doi: 10.1186/s12943-020-01223-4.
Ref 5 N6-methyladenosine demethylase FTO promotes growth and metastasis of gastric cancer via m(6)A modification of caveolin-1 and metabolic regulation of mitochondrial dynamics. Cell Death Dis. 2022 Jan 21;13(1):72. doi: 10.1038/s41419-022-04503-7.
Ref 6 Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer. J Adv Res. 2021 Oct 5;37:91-106. doi: 10.1016/j.jare.2021.10.001. eCollection 2022 Mar.
Ref 7 Omeprazole improves chemosensitivity of gastric cancer cells by m6A demethylase FTO-mediated activation of mTORC1 and DDIT3 up-regulation. Biosci Rep. 2021 Jan 29;41(1):BSR20200842. doi: 10.1042/BSR20200842.
Ref 8 METTL3 Promotes the Progression of Gastric Cancer via Targeting the MYC Pathway. Front Oncol. 2020 Feb 26;10:115. doi: 10.3389/fonc.2020.00115. eCollection 2020.
Ref 9 YTHDF1 Promotes Gastric Carcinogenesis by Controlling Translation of FZD7. Cancer Res. 2021 May 15;81(10):2651-2665. doi: 10.1158/0008-5472.CAN-20-0066. Epub 2020 Aug 11.
Ref 10 METTL16 promotes cell proliferation by up-regulating cyclin D1 expression in gastric cancer. J Cell Mol Med. 2021 Jul;25(14):6602-6617. doi: 10.1111/jcmm.16664. Epub 2021 Jun 2.
Ref 11 METTL3-mediated m(6)A modification of HDGF mRNA promotes gastric cancer progression and has prognostic significance. Gut. 2020 Jul;69(7):1193-1205. doi: 10.1136/gutjnl-2019-319639. Epub 2019 Oct 3.
Ref 12 N(6)-methyladenosine (m(6)A) methyltransferase WTAP accelerates the Warburg effect of gastric cancer through regulating HK2 stability. Biomed Pharmacother. 2021 Jan;133:111075. doi: 10.1016/j.biopha.2020.111075. Epub 2020 Dec 9.
Ref 13 HOXB13 promotes gastric cancer cell migration and invasion via IGF-1R upregulation and subsequent activation of PI3K/AKT/mTOR signaling pathway. Life Sci. 2021 Aug 1;278:119522. doi: 10.1016/j.lfs.2021.119522. Epub 2021 Apr 21.
Ref 14 Knockdown of m6A Reader IGF2BP3 Inhibited Hypoxia-Induced Cell Migration and Angiogenesis by Regulating Hypoxia Inducible Factor-1Alpha in Stomach Cancer. Front Oncol. 2021 Sep 21;11:711207. doi: 10.3389/fonc.2021.711207. eCollection 2021.
Ref 15 IGF2BP2 promotes gastric cancer progression by regulating the IGF1R-RhoA-ROCK signaling pathway. Cell Signal. 2022 Jun;94:110313. doi: 10.1016/j.cellsig.2022.110313. Epub 2022 Mar 16.
Ref 16 N(6)-Methyladenosine RNA Demethylase FTO Promotes Gastric Cancer Metastasis by Down-Regulating the m6A Methylation of ITGB1. Front Oncol. 2021 Jul 1;11:681280. doi: 10.3389/fonc.2021.681280. eCollection 2021.
Ref 17 Loss of YTHDF1 in gastric tumors restores sensitivity to antitumor immunity by recruiting mature dendritic cells. J Immunother Cancer. 2022 Feb;10(2):e003663. doi: 10.1136/jitc-2021-003663.
Ref 18 METTL3-mediated m(6)A methylation of SPHK2 promotes gastric cancer progression by targeting KLF2. Oncogene. 2021 Apr;40(16):2968-2981. doi: 10.1038/s41388-021-01753-1. Epub 2021 Mar 23.
Ref 19 The m6A Methyltransferase METTL14-Mediated N6-Methyladenosine Modification of PTEN mRNA Inhibits Tumor Growth and Metastasis in Stomach Adenocarcinoma. Front Oncol. 2021 Aug 12;11:699749. doi: 10.3389/fonc.2021.699749. eCollection 2021.
Ref 20 HBXIP promotes gastric cancer via METTL3-mediated MYC mRNA m6A modification. Aging (Albany NY). 2020 Oct 13;12(24):24967-24982. doi: 10.18632/aging.103767. Epub 2020 Oct 13.
Ref 21 N(6)-methyladenosine (m(6)A) reader IGF2BP1 accelerates gastric cancer aerobic glycolysis in c-Myc-dependent manner. Exp Cell Res. 2022 Aug 1;417(1):113176. doi: 10.1016/j.yexcr.2022.113176. Epub 2022 Apr 27.
Ref 22 Demethylase ALKBH5 suppresses invasion of gastric cancer via PKMYT1 m6A modification. Mol Cancer. 2022 Feb 3;21(1):34. doi: 10.1186/s12943-022-01522-y.
Ref 23 N(6)-methyladenosine (m(6)A) reader IGF2BP2 promotes gastric cancer progression via targeting SIRT1. Bioengineered. 2022 May;13(5):11541-11550. doi: 10.1080/21655979.2022.2068920.
Ref 24 The m6A methyltransferase METTL14 inhibits the proliferation, migration, and invasion of gastric cancer by regulating the PI3K/AKT/mTOR signaling pathway. J Clin Lab Anal. 2021 Mar;35(3):e23655. doi: 10.1002/jcla.23655. Epub 2020 Dec 12.
Ref 25 METTL3 promotes oxaliplatin resistance of gastric cancer CD133+?stem cells by promoting PARP1 mRNA stability. Cell Mol Life Sci. 2022 Feb 18;79(3):135. doi: 10.1007/s00018-022-04129-0.
Ref 26 METTL14-mediated m(6)A modification of circORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p/AKT1S1 axis. Mol Cancer. 2022 Feb 14;21(1):51. doi: 10.1186/s12943-022-01521-z.
Ref 27 Impaired autophagic degradation of lncRNA ARHGAP5-AS1 promotes chemoresistance in gastric cancer. Cell Death Dis. 2019 May 16;10(6):383. doi: 10.1038/s41419-019-1585-2.
Ref 28 M(6) A demethylase fat mass and obesity-associated protein regulates cisplatin resistance of gastric cancer by modulating autophagy activation through ULK1. Cancer Sci. 2022 Jun 22. doi: 10.1111/cas.15469. Online ahead of print.
Ref 29 Knockdown of m6A methyltransferase METTL3 in gastric cancer cells results in suppression of cell proliferation. Oncol Lett. 2020 Sep;20(3):2191-2198. doi: 10.3892/ol.2020.11794. Epub 2020 Jul 1.
Ref 30 RNA N6-methyladenosine modification participates in miR-660/E2F3 axis-mediated inhibition of cell proliferation in gastric cancer. Pathol Res Pract. 2019 Jun;215(6):152393. doi: 10.1016/j.prp.2019.03.021. Epub 2019 Mar 19.
Ref 31 KIAA1429 regulates cell proliferation by targeting c-Jun messenger RNA directly in gastric cancer. J Cell Physiol. 2020 Oct;235(10):7420-7432. doi: 10.1002/jcp.29645. Epub 2020 Feb 13.
Ref 32 The N6-methyladenosine reader protein YTHDC2 promotes gastric cancer progression via enhancing YAP mRNA translation. Transl Oncol. 2022 Feb;16:101308. doi: 10.1016/j.tranon.2021.101308. Epub 2021 Dec 12.
Ref 33 m6A Methyltransferase 3 Promotes the Proliferation and Migration of Gastric Cancer Cells through the m6A Modification of YAP1. J Oncol. 2021 Aug 4;2021:8875424. doi: 10.1155/2021/8875424. eCollection 2021.
Ref 34 MiR-4429 prevented gastric cancer progression through targeting METTL3 to inhibit m(6)A-caused stabilization of SEC62. Biochem Biophys Res Commun. 2019 Oct 1;517(4):581-587. doi: 10.1016/j.bbrc.2019.07.058. Epub 2019 Aug 5.
Ref 35 The m(6)A Reader YTHDF1 Facilitates the Tumorigenesis and Metastasis of Gastric Cancer via USP14 Translation in an m(6)A-Dependent Manner. Front Cell Dev Biol. 2021 Mar 15;9:647702. doi: 10.3389/fcell.2021.647702. eCollection 2021.
Ref 36 METTL3-mediated N6-methyladenosine modification is critical for epithelial-mesenchymal transition and metastasis of gastric cancer. Mol Cancer. 2019 Oct 13;18(1):142. doi: 10.1186/s12943-019-1065-4.
Ref 37 N6-Methyladenosine Related Long Non-Coding RNAs and Immune Cell Infiltration in the Tumor Microenvironment of Gastric Cancer. Biol Proced Online. 2021 Aug 1;23(1):15. doi: 10.1186/s12575-021-00152-w.
Ref 38 N6-methyladenosine (m6A)-mediated up-regulation of long noncoding RNA LINC01320 promotes the proliferation, migration, and invasion of gastric cancer via miR495-5p/RAB19 axis. Bioengineered. 2021 Dec;12(1):4081-4091. doi: 10.1080/21655979.2021.1953210.
Ref 39 LncRNA LINC00470 promotes the degradation of PTEN mRNA to facilitate malignant behavior in gastric cancer cells. Biochem Biophys Res Commun. 2020 Jan 22;521(4):887-893. doi: 10.1016/j.bbrc.2019.11.016. Epub 2019 Nov 8.
Ref 40 m(6) A transferase KIAA1429-stabilized LINC00958 accelerates gastric cancer aerobic glycolysis through targeting GLUT1. IUBMB Life. 2021 Nov;73(11):1325-1333. doi: 10.1002/iub.2545. Epub 2021 Aug 26.
Ref 41 ALKBH5 promotes invasion and metastasis of gastric cancer by decreasing methylation of the lncRNA NEAT1. J Physiol Biochem. 2019 Aug;75(3):379-389. doi: 10.1007/s13105-019-00690-8. Epub 2019 Jul 9.
Ref 42 lncRNA THAP7-AS1, transcriptionally activated by SP1 and post-transcriptionally stabilized by METTL3-mediated m6A modification, exerts oncogenic properties by improving CUL4B entry into the nucleus. Cell Death Differ. 2022 Mar;29(3):627-641. doi: 10.1038/s41418-021-00879-9. Epub 2021 Oct 4.
Ref 43 Down-regulation of circPVRL3 promotes the proliferation and migration of gastric cancer cells. Sci Rep. 2018 Jul 4;8(1):10111. doi: 10.1038/s41598-018-27837-9.
Ref 44 Circular RNA expression profile and m6A modification analysis in poorly differentiated adenocarcinoma of the stomach. Epigenomics. 2020 Jun;12(12):1027-1040. doi: 10.2217/epi-2019-0153. Epub 2020 Jul 13.
Ref 45 N(6)-methyladenosine-dependent pri-miR-17-92 maturation suppresses PTEN/TMEM127 and promotes sensitivity to everolimus in gastric cancer. Cell Death Dis. 2020 Oct 9;11(10):836. doi: 10.1038/s41419-020-03049-w.