The m6A-binding protein YTHDC2 affects proliferation and apoptosis of colorectal cancer cells by regulating the p38MAPK signaling pathway

doi:10.3877/cma.j.issn.2095-3224.2023.02.005

Abstract

Abstract:

Objective

To investigate the molecular mechanism and signal pathway of m⁶A binding protein YTHDC2 in the development of colorectal cancer.

Methods

The relationship between YTHDC2 and colorectal cancer in the Cancer Genome Atlas (TCGA) database was analyzed through The Human Protein Atlas and GEPIA websites, and the related signal transduction pathways and biological processes were explored. Colorectal cancer cell lines HCT116 and Caco2 were cultured in vitro. After YTHDC2 was overexpressed or knocked down, the expression of p38MAPK, p-p38MAPK and their downstream apoptosis-related proteins in the mitogen-activated protein kinase (MAPK) signaling pathway was detected by RT-PCR and Western blot. The apoptosis rate was detected by flow cytometry.

Results

The Human Protein Atlas and GEPIA analysis results showed that the expression level of YTHDC2 in tumor tissues was lower than that in adjacent tissues, and the increase of YTHDC2 expression was positively correlated with the improvement of overall survival rate of patients with colorectal cancer. Based on the gene expression and clinical data related to colorectal cancer in cBioPortal and Xena databases and the annotated gene sets in KEGG and GO databases, gene set enrichment analysis (GSEA) suggested that YTHDC2 had a role in regulating the MAPK signaling pathway. The results of flow cytometry showed that the apoptosis rate was significantly reduced in YTHDC2 knockout group and increased in YTHDC2 overexpression group. Western blot showed that the expression of p38MAPK did not change significantly, while p-p38MAPK was significantly increased in YTHDC2 overexpression group and decreased in YTHDC2 knockout group. The results of gene expression profile interaction analysis (GEPIA) suggested that the expression of apoptotic proteins was positively correlated with the expression of YTHDC2, which was consistent with the results of RT-PCR and Western blot.

Conclusions

YTHDC2 activates exogenous death receptors and endogenous mitochondrial apoptosis pathways in the p38MAPK signaling pathway to regulate the apoptosis of colorectal cancer cells.

Key words: Colorectal neoplasms, Post-transcriptional modification, Apoptosis, YTHDC2 protein, N-methyladenosine

Shiyao Zhang, Yanyan Xu, Qi Zhang, Chunqiang Li, Zhicheng Zhao, Gang Liu. The m⁶A-binding protein YTHDC2 affects proliferation and apoptosis of colorectal cancer cells by regulating the p38MAPK signaling pathway[J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2023, 12(02): 117-124.

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The m⁶A-binding protein YTHDC2 affects proliferation and apoptosis of colorectal cancer cells by regulating the p38MAPK signaling pathway

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