Inhibition of TRIM32 Induced by miR-519d Increases the Sensitivity of Colorectal Cancer Cells to Cisplatin

Abstract

Xueliang Su, 1 Bangjie Wang, 2 Yehong Wang, 2 Baochun Wang 2 1General Surgery, Danzhou People’s Hospital, Danzhou City, Hainan Province 571700, People’s Republic of China; 2Department of General Surgery, Hainan General Hospital, Haikou City, Hainan Province 570311, People’s Republic of ChinaCorrespondence: Baochun Wang No. 19, Xiuhua Road, Xiuying District, Haikou City, Hainan Province 570311, People’s Republic of ChinaEmail [email protected]: Colorectal cancer is a leading cause of cancer-related death in the world. Despite cisplatin is a commonly used chemotherapeutic drug for the colorectal cancer treatment, resistance of cancer cells to cisplatin restricts its clinical efficacy. It is important to explore the potential mechanisms and take strategies to sensitize colorectal cancer cells to cisplatin treatment.Methods: Differences of TRIM32 and miR-519d expression between colorectal cancer cells and human normal colon epithelial cells were evaluated by qRT-PCR and Western blot assays. Cytotoxicity of cisplatin against colorectal cancer cells was tested by CCK-8 assay. Generation of reactive oxygen species (ROS), mitochondrial membrane potential and apoptosis was measured by flow cytometry. Dual-luciferase reporter assay was used to validate the association between miR-519d and TRIM32.Results: Significant increase of TRIM32 expression in colorectal cancer tissues and cell lines was observed. TRIM32 negatively regulated the cisplatin sensitivity in colorectal cancer cells. Mechanically, overexpression of TRIM32 was induced by decrease of miR-519d. Exogenous miR-519d can inhibit the expression of TRIM32 and thus promoted the cisplatin-induced apoptosis through the mitochondrial pathway.Conclusion: Overexpression of TRIM32 was induced by the absence of miR-519d in colorectal cancer. MiR-519d can be used as a sensitizer during the cisplatin-based chemotherapy of colorectal cancer.Keywords: miR-519d, TRIM32, cisplatin, colorectal cancer

Keywords

• mir-519d
• trim32
• cisplatin
• colorectal cancer