• DNMT3B is overexpressed in colorectal cancer tissues and cell lines, correlating with poor prognosis.
• DNMT3B promotes colorectal cancer cell proliferation by hypermethylating the PLCG2 promoter, thereby silencing PLCG2 expression.
• Overexpression of PLCG2 suppresses colorectal cancer xenograft tumor growth in vivo, confirming its tumor-suppressive role.
• Targeting the DNMT3B-PLCG2 axis offers a novel therapeutic strategy for colorectal cancer treatment.