Targeting BMI1 enhances cell adhesion to inhibit colorectal cancer progression and improve the efficacy of cetuximab

Abstract Colorectal cancer (CRC) is a common malignant tumor with poor prognosis, urgently requiring new biomarkers and therapeutic targets. This study investigated the role of BMI1 in the progression of colorectal cancer and its regulatory mechanisms, as well as evaluated whether targeting BMI1 can enhance the efficacy of first-line drugs. BMI1 is highly expressed in colorectal cancer and promotes malignant progression by inhibiting cell adhesion. Knockdown of BMI1 suppresses its malignant behavior in both in vitro and in vivo experiments. MiR-218-5p targets the 3' UTR region of BMI1 and is downregulated in CRC; overexpression of miR-218-5p can reverse BMI1-mediated CRC progression. Furthermore, resveratrol targets and inhibits BMI1, thereby sensitizing CRC cells to the first-line EGFR-targeted drug cetuximab. The combination of resveratrol and cetuximab exhibits synergistic antitumor effects both in cultured cells and in vivo. In summary, this study elucidates the intervention role of miR-218-5p as an upstream regulator of BMI1 and confirms that resveratrol’s targeted inhibition of BMI1 can enhance the therapeutic effect of cetuximab, providing new experimental evidence and strategies for molecular targeted combination therapy in colorectal cancer.