YTHDC2 Promotes the Apoptosis of Colorectal Cancer Cells Through the p38MAPK Signaling Pathway

Abstract Background The role of the m6A-binding protein YTHDC2 in the occurrence and development of colorectal cancer (CRC) is unclear. We aimed to explore the molecular mechanisms underlying this process and clarify the signaling pathway involved. Methods Firstly, the relationship between YTHDC2 and CRC in TCGA database was analyzed to identify relevant signaling pathways and biological processes. Then, western blot was used to analyze expression of YTHDC2 in HCT116 and Caco2 cells. After knockdown or overexpression of YTHDC2 in the above cells, RT-PCR and western blot were used to analyze p38MAPK, p-p38MAPK, and downstream apoptosis-related proteins in the MAPK signaling pathway. Flow cytometry was performed to detect changes in apoptosis. Results And the results were shown that the expression of YTHDC2 was significantly lower in tumor tissues than in normal tissues. Increased expression of YTHDC2 was associated with better overall survival among patients with CRC. Gene set enrichment analysis revealed that YTHDC2 regulates the MAPK signaling pathway. Flow cytometry revealed apoptosis was significantly reduced and enhanced in response to YTHDC2 knockdown and overexpression, respectively. There was no significant change in the expression of p38MAPK, while p-p38MAPK was significantly increased in response to overexpression and decreased in response to knockdown. Gene Expression Profiling Interactive Analysis showed apoptotic protein expression to be positively correlated with YTHDC2 expression, consistent with the results of RT-PCR and western blot. Conclusion In general, apoptosis of CRC cells is promoted by YTHDC2 via activation of the exogenous death receptor and endogenous mitochondrial apoptosis-related pathways in the p38MAPK signaling pathway.