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
Ref 1 An N(6)-methyladenosine at the transited codon 273 of p53 pre-mRNA promotes the expression of R273H mutant protein and drug resistance of cancer cells. Biochem Pharmacol. 2019 Feb;160:134-145. doi: 10.1016/j.bcp.2018.12.014. Epub 2018 Dec 19.
Ref 2 Gb3-cSrc complex in glycosphingolipid-enriched microdomains contributes to the expression of p53 mutant protein and cancer drug resistance via Beta-catenin-activated RNA methylation. FASEB Bioadv. 2020 Sep 2;2(11):653-667. doi: 10.1096/fba.2020-00044. eCollection 2020 Nov.
Ref 3 m(6)A modification-mediated CBX8 induction regulates stemness and chemosensitivity of colon cancer via upregulation of LGR5. Mol Cancer. 2019 Dec 18;18(1):185. doi: 10.1186/s12943-019-1116-x.
Ref 4 hnRNPA2B1 Promotes Colon Cancer Progression via the MAPK Pathway. Front Genet. 2021 Sep 22;12:666451. doi: 10.3389/fgene.2021.666451. eCollection 2021.
Ref 5 RNA helicase YTHDC2 promotes cancer metastasis via the enhancement of the efficiency by which HIF-1Alpha mRNA is translated. Cancer Lett. 2016 Jun 28;376(1):34-42. doi: 10.1016/j.canlet.2016.02.022. Epub 2016 Mar 17.
Ref 6 Targeting YTHDF1 effectively re-sensitizes cisplatin-resistant colon cancer cells by modulating GLS-mediated glutamine metabolism. Mol Ther Oncolytics. 2021 Jan 16;20:228-239. doi: 10.1016/j.omto.2021.01.001. eCollection 2021 Mar 26.
Ref 7 m6A methyltransferase METTL3 maintains colon cancer tumorigenicity by suppressing SOCS2 to promote cell proliferation. Oncol Rep. 2020 Sep;44(3):973-986. doi: 10.3892/or.2020.7665. Epub 2020 Jun 26.
Ref 8 RNA N6-methyladenosine reader IGF2BP3 regulates cell cycle and angiogenesis in colon cancer. J Exp Clin Cancer Res. 2020 Sep 29;39(1):203. doi: 10.1186/s13046-020-01714-8.
Ref 9 Integrative Analysis Reveals Potentially Functional N6-Methylandenosine-Related Long Noncoding RNAs in Colon Adenocarcinoma. Front Genet. 2021 Sep 17;12:739344. doi: 10.3389/fgene.2021.739344. eCollection 2021.