Methyltransferase DNMT3B promotes colorectal cancer cell proliferation by inhibiting PLCG2

Abstract Background Aberrant DNA methylation patterns in the promoter region of PLCG2 have been associated with dysregulated signaling pathways and cellular functions. Its role in colorectal cancer cells is still unknown. Methods qRT-PCR was used to examine DNMT3B expression in colorectal cancer. Western blot and immunohistochemistry were used to analyze DNMT3B and PLCG2 protein levels in colorectal tissues and cell lines. The cell counting kit-8 and colony experiments were used to identify the proliferation of colorectal cancer cells. Methylation-specific PCR (MSP) and bisulfite-sequencing PCR (BSP) was used to measure DNA methylation levels. Results DNMT3B is overexpressed in colorectal cell in TCGA datasets and Kaplan-Meier plots. DNMT3B is significantly overexpressed in tumor tissues compared to adjacent non-tumor tissues. Western blotting results demonstrated high expression of DNMT3B in tumor tissues. Compared to normal colonic epithelial cells, colorectal cancer cell lines exhibited elevated levels of PLCG2 methylation. oePLCG2 effectively prevented the in vivo xenograft tumor growth of colorectal cancer. Conclusions PLCG2 is identified as a key downstream regulatory protein of DNMT3B in colorectal cancer. DNMT3B Inhibits PLCG2 transcription through methylation of the PLCG2 promoter region. DNMT3B controls colorectal cancer cell proliferation through the PLCG2, which is useful for creating therapeutic approaches that target PLCG2 expression for the treatment of colorectal cancer.