miR-188 promotes Oxaliplatin resistances through targeting RASA1 in colon cancer cells

Abstract

Background: One main drawback of chemotherapy application in colon cancer clinically is drug resistance. miR-188-5p has been shown to be down-regulated in various types of cancer. The aim of this study was to explore the molecular mechanism of miR-188-5p in drug resistant cancer cells. Methods: we examined the effects of miR-188-5p on the sensitivity of colon cancer cells to oxaliplatin (OXA) by using SW480/OXA cell line. The target of miR-188-5p was determined by luciferase activity assay. The cell cycle distribution were detected by flow cytometry. The expression of p21, Hoechst 33342 staining and Annexin V assays were used to detect the cell apoptosis. Results: The expression of miR-188-5p was significantly increased in SW480/OXA cells compared with SW480 cells. By luciferase assay we found that miR-188-5p miRNA binds to RASA1 (Ras GTPase-activating protein 1, also known as p120RasGAP), and overexpression of miR-188-5p inhibited RASA1 expression by binding to the 3'-untranslated region of RASA1 mRNA. In addition, suppression of miR-188-5p enhanced the chemosensitivity of the oxaliplatin-resistant colon cancer cells. Furthermore, suppression of RASA1 abrogated the increasement of cell apoptosis induced by miR-188-5p inhibitor, while, overexpression of RASA1 induced cell apoptosis in SW480/OXA cells. Our results suggested that miR-188-5p played chemoresistant role in colon cancer through regulating RASA1 expression. Conclusion: The findings of our study suggest that target miR-188-5p is capable of enhancing the chemosensitivity of colon cancer cells by promoting RASA1.