m6A-centered Disease Response Information
General Information of the Disease (ID: M6ADIS0058)
Name |
Colon cancer
|
||||
---|---|---|---|---|---|
ICD |
ICD-11: 2B90
|
Full List of Target Gene(s) of This m6A-centered Disease Response
Cellular tumor antigen p53 (TP53/p53)
In total 2 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [1] | |||
Response Summary | The produced p53 R273H mutant protein resulted in acquired multidrug resistance in colon cancer cells. Either silencing METTL3 expression by using small interfering RNA (siRNA) or inhibiting RNA methylation with neplanocin A suppressed m6A formation in Cellular tumor antigen p53 (TP53/p53) pre-mRNA, and substantially increased the level of phosphorylated p53 protein (Ser15) and its function in cells heterozygously carrying the R273H mutation, thereby re-sensitizing these cells to anticancer drugs. | |||
Responsed Disease | Colon cancer [ICD-11: 2B90] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Up regulation | |||
Pathway Response | p53 signaling pathway | hsa04115 | ||
Cell Process | Protein signaling | |||
In-vitro Model | SW480 | Colon adenocarcinoma | Homo sapiens | CVCL_0546 |
WiDr | Colon adenocarcinoma | Homo sapiens | CVCL_2760 | |
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene | [2] | |||
Response Summary | Colon cancer cell lines, either WiDr homozygous for missense-mutated Cellular tumor antigen p53 (TP53/p53) (R273H) or SW48/TP53-Dox bearing heterozygous TP53 mutant (R273H), display drug resistance with increased ceramide glycosylation. Increased Gb3-cSrc complex in GEMs of membranes in response to anticancer drug induced cell stress promotes expression of p53 mutant proteins and accordant cancer drug resistance. Genz-161 effectively inhibited GCS activity, and substantially suppressed the elevated Gb3 levels seen in GEMs of p53-mutant cells exposed to doxorubicin. | |||
Responsed Disease | Colon cancer [ICD-11: 2B90] | |||
Pathway Response | Apoptosis | hsa04210 | ||
Wnt signaling pathway | hsa04310 | |||
Cell Process | Cellular stress | |||
Cell apoptosis | ||||
In-vitro Model | SW480 | Colon adenocarcinoma | Homo sapiens | CVCL_0546 |
In-vivo Model | Cell suspension of SW48 or SW48/TP53 (5-7 passages, 1 × 106 cells in 20 uL/mouse) was subcutaneously injected into the left flank of the mice. | |||
Chromobox protein homolog 8 (CBX8)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [3] | |||
Response Summary | m6A methylation participated in the upregulation of CBX8 by maintaining Chromobox protein homolog 8 (CBX8) mRNA stability. Upon m6A methylation-induced upregulation, CBX8 interacts with KMT2b and Pol II to promote LGR5 expression in a noncanonical manner, which contributes to increased cancer stemness and decreased chemosensitivity in colon cancer. | |||
Responsed Disease | Colon cancer [ICD-11: 2B90] | |||
Cell Process | Stemness property | |||
In-vitro Model | LoVo | Colon adenocarcinoma | Homo sapiens | CVCL_0399 |
SW620 | Colon adenocarcinoma | Homo sapiens | CVCL_0547 | |
SW480 | Colon adenocarcinoma | Homo sapiens | CVCL_0546 | |
DLD-1 | Colon adenocarcinoma | Homo sapiens | CVCL_0248 | |
COLO 205 | Colon adenocarcinoma | Homo sapiens | CVCL_0218 | |
HT-29 | Colon adenocarcinoma | Homo sapiens | CVCL_0320 | |
HCT 116 | Colon carcinoma | Homo sapiens | CVCL_0291 | |
NCM460 | Normal | Homo sapiens | CVCL_0460 | |
In-vivo Model | Xenograft tumor formation was observed in 5 of 5 and 3 of 5 animals when 1 × 105 and 1 × 104 sorted LGR5+ cells, were subcutaneously injected into nude mice, respectively | |||
Ephrin type-B receptor 2 (ERK/EPHB2)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [4] | |||
Response Summary | hnRNPA2B1 promotes colon cancer progression via the MAPK pathway. hnRNPA2B1 is an upstream regulator of the Ephrin type-B receptor 2 (ERK/EPHB2)/MAPK pathway and inhibition of MAPK signaling blocked the effects of hnRNPA2B1. | |||
Responsed Disease | Colon cancer [ICD-11: 2B90] | |||
Target Regulator | Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) | READER | ||
Target Regulation | Up regulation | |||
Pathway Response | MAPK signaling | hsa04010 | ||
Apoptosis | hsa04210 | |||
Cell Process | Arrest cell cycle at G0/G1 phase | |||
Cell apoptosis | ||||
In-vitro Model | HCT 116 | Colon carcinoma | Homo sapiens | CVCL_0291 |
SW480 | Colon adenocarcinoma | Homo sapiens | CVCL_0546 | |
In-vivo Model | Four-week-old male BALB/c nude mice (purchased from Lingchang company) were randomly divided into three groups, each group has five mice. Each of the mice was injected subcutaneously on the right lateral back with 1 × 106 of each lentivirus infected SW480 cells in which hnRNPA2B1 was knocked out or negative control cells. Mice were killed at day 29, and tumors were then isolated, photographed. | |||
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 | [5] | |||
Response Summary | YTHDC2 contributes to colon tumor metastasis by promoting translation of Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A) and that YTHDC2 is potentially a diagnostic marker and target gene for treating colon cancer patients. | |||
Responsed Disease | Colon cancer [ICD-11: 2B90] | |||
Target Regulator | YTH domain-containing protein 2 (YTHDC2) | READER | ||
Target Regulation | Up regulation | |||
Pathway Response | HIF-1 signaling pathway | hsa04066 | ||
Cell Process | Biological regulation | |||
In-vitro Model | COS (From the African green monkey cell line (CV-1).) | |||
HCT 116 | Colon carcinoma | Homo sapiens | CVCL_0291 | |
HT29 | Colon cancer | Mus musculus | CVCL_A8EZ | |
In-vivo Model | HCT116, Y2KD-116 and con-116 cells were resuspended at 1 × 106 cells per 50 ul of PBS. Cells were injected into the exteriorized spleen after abdominal incision. | |||
Mammalian target of rapamycin complex 2 (mTORC2)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [6] | |||
Response Summary | YTHDF1-promoted cisplatin resistance, contributing to overcoming chemoresistant colon cancers. | |||
Responsed Disease | Colon cancer [ICD-11: 2B90] | |||
Responsed Drug | Cisplatin | Approved | ||
Target Regulator | YTH domain-containing family protein 1 (YTHDF1) | READER | ||
Pathway Response | Metabolic pathways | hsa01100 | ||
Cell Process | Glutamine metabolism | |||
In-vitro Model | LoVo | Colon adenocarcinoma | Homo sapiens | CVCL_0399 |
HT-29 | Colon adenocarcinoma | Homo sapiens | CVCL_0320 | |
DLD-1 | Colon adenocarcinoma | Homo sapiens | CVCL_0248 | |
HCT 116 | Colon carcinoma | Homo sapiens | CVCL_0291 | |
SW480 | Colon adenocarcinoma | Homo sapiens | CVCL_0546 | |
CRL-1790 (The normal colon epithelial cell line CRL-1790, were purchased from the American Type Culture Collection (ATCC).) | ||||
In-vivo Model | Mice were injected subcutaneously with LoVo (1 × 106) cells, which were stably transfected with the control shRNA or YTHDF1 shRNA. | |||
Mitogen-activated protein kinase 1 (MAPK/ERK2/MAPK1)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [4] | |||
Response Summary | hnRNPA2B1 promotes colon cancer progression via the MAPK pathway. hnRNPA2B1 is an upstream regulator of the ERK/Mitogen-activated protein kinase 1 (MAPK/ERK2/MAPK1) pathway and inhibition of MAPK signaling blocked the effects of hnRNPA2B1. | |||
Responsed Disease | Colon cancer [ICD-11: 2B90] | |||
Target Regulator | Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) | READER | ||
Target Regulation | Up regulation | |||
Pathway Response | MAPK signaling | hsa04010 | ||
Cell Process | Arrest cell cycle at G0/G1 phase | |||
Cell apoptosis | ||||
In-vitro Model | HCT 116 | Colon carcinoma | Homo sapiens | CVCL_0291 |
SW480 | Colon adenocarcinoma | Homo sapiens | CVCL_0546 | |
In-vivo Model | Four-week-old male BALB/c nude mice (purchased from Lingchang company) were randomly divided into three groups, each group has five mice. Each of the mice was injected subcutaneously on the right lateral back with 1 × 106 of each lentivirus infected SW480 cells in which hnRNPA2B1 was knocked out or negative control cells. Mice were killed at day 29, and tumors were then isolated, photographed. | |||
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 | [7] | |||
Response Summary | An increased level of METTL3 may maintain the tumorigenicity of colon cancer cells by suppressing Suppressor of cytokine signaling 2 (SOCS2). | |||
Responsed Disease | Colon cancer [ICD-11: 2B90] | |||
Target Regulator | Methyltransferase-like 3 (METTL3) | WRITER | ||
Target Regulation | Down regulation | |||
Cell Process | Cell proliferation | |||
In-vitro Model | SW480 | Colon adenocarcinoma | Homo sapiens | CVCL_0546 |
Vascular endothelial growth factor A (VEGFA)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [8] | |||
Response Summary | Knockdown of IGF2BP3 repressed DNA replication in the S phase of cell cycle and angiogenesis via reading m6A modification of CCND1 and Vascular endothelial growth factor A (VEGFA) respectively. Knockdown of IGF2BP3 repressed angiogenesis in colon cancer via regulating VEGF. | |||
Responsed Disease | Colon cancer [ICD-11: 2B90] | |||
Target Regulator | Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) | READER | ||
Target Regulation | Up regulation | |||
Pathway Response | Cell cycle | hsa04110 | ||
VEGF signaling pathway | hsa04370 | |||
Cell Process | Arrest cell cycle at S phase | |||
In-vitro Model | SW620 | Colon adenocarcinoma | Homo sapiens | CVCL_0547 |
SW480 | Colon adenocarcinoma | Homo sapiens | CVCL_0546 | |
SW1116 | Colon adenocarcinoma | Homo sapiens | CVCL_0544 | |
RKO | Colon carcinoma | Homo sapiens | CVCL_0504 | |
LoVo | Colon adenocarcinoma | Homo sapiens | CVCL_0399 | |
HT29 | Colon cancer | Mus musculus | CVCL_A8EZ | |
HCT 116 | Colon carcinoma | Homo sapiens | CVCL_0291 | |
In-vivo Model | All the mice (n = 12) were equally and randomly divided into the HCT-scr and HCT-shMETTL3 group. 3 × 106 HCT-scr or HCT-shIGF2BP3 cells suspended in 100 uL PBS were injected subcutaneously from the axilla of each nude mice. After 1 weeks, the long (L) and short (S) diameter of the tumors were measured with vernier caliper every 3 days (tumor volume = L*S2/2). The growth curve of subcutaneous tumors was drawn on the basis of the measured tumor volume. All mice were killed after 17 days since injection of colon cancer cells and subcutaneous tumors were removed completely. | |||
Long intergenic non-protein coding RNA 2604 (LINC02604/RP11-458F8.4)
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [9] | |||
Response Summary | Identified 10 upregulated m6A regulators at both mRNA and protein levels, and 2,479 m6A-related lncRNAs in colon adenocarcinoma. Functional inference suggested that CTD-3184A7.4, Long intergenic non-protein coding RNA 2604 (LINC02604/RP11-458F8.4), and RP11-108L7.15 were positively correlated with the energy metabolism-related pathways, further suggesting that these lncRNAs were involved in energy metabolism-related pathways. | |||
Responsed Disease | Colon adenocarcinoma [ICD-11: 2B90.Y] | |||
Cell Process | Energy metabolism | |||
CTD-3184A7.4
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [9] | |||
Response Summary | Identified 10 upregulated m6A regulators at both mRNA and protein levels, and 2,479 m6A-related lncRNAs in colon adenocarcinoma. Functional inference suggested that CTD-3184A7.4, RP11-458F8.4, and RP11-108L7.15 were positively correlated with the energy metabolism-related pathways, further suggesting that these lncRNAs were involved in energy metabolism-related pathways. | |||
Responsed Disease | Colon adenocarcinoma [ICD-11: 2B90.Y] | |||
Cell Process | Energy metabolism | |||
RP11-108L7.15
In total 1 item(s) under this target gene | ||||
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene | [9] | |||
Response Summary | Identified 10 upregulated m6A regulators at both mRNA and protein levels, and 2,479 m6A-related lncRNAs in colon adenocarcinoma. Functional inference suggested that CTD-3184A7.4, RP11-458F8.4, and RP11-108L7.15 were positively correlated with the energy metabolism-related pathways, further suggesting that these lncRNAs were involved in energy metabolism-related pathways. | |||
Responsed Disease | Colon adenocarcinoma [ICD-11: 2B90.Y] | |||
Cell Process | Energy metabolism | |||
References