miR‑188‑5p promotes oxaliplatin resistance by targeting RASA1 in colon cancer cells

Abstract

The efficacy of chemotherapy for colon cancer is limited due to the development of chemoresistance. MicroRNA (miR)‑188‑5p is downregulated in various types of cancer. The aim of the present study was to explore the molecular role of miR‑188 in oxaliplatin (OXA) resistance. An OXA‑resistant colon cancer cell line, SW480/OXA, was used to examine the effects of miR‑188‑5p on the sensitivity of colon cancer cells to OXA. The target of miR‑188‑5p was identified using a luciferase assay. Cell cycle distribution was also assessed using flow cytometry. The measurement of p21 protein expression, Hoechst 33342 staining and Annexin V/propidium iodide staining was used to evaluate apoptosis. The expression of miR‑188‑5p significantly increased in SW480/OXA compared with wild‑type SW480 cells. The luciferase assay demonstrated that miR‑188‑5p inhibited Ras GTPase‑activating protein 1 (RASA1; also known as p120/RasGAP) luciferase activity by binding to the 3'‑untranslated region of RASA1 mRNA, suggesting that miR‑188‑5p could target RASA1. In addition, miR‑188‑5p downregulation or RASA1 over­expression promoted the chemosensitivity of SW480/OXA, as evidenced by increased apoptosis and G1/S cell cycle arrest. Moreover, RASA1 silencing abrogated the increase in cell apoptosis induced by the miR‑188‑5p inhibitor. The findings of the present study suggested that miR‑188‑5p could enhance colon cancer cell chemosensitivity by promoting the expression of RASA1.