m6A-centered Disease Response Information
General Information of the Disease (ID: M6ADIS0057)
Name |
Gastric cancer
|
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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 | |
CBSLR
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