MicroRNA-192 acts as a tumor suppressor in colon cancer and simvastatin activates miR-192 to inhibit cancer cell growth

Abstract

Colon cancer is one of the most common malignant tumors worldwide. Understanding the underlying molecular mechanisms is crucial for the development of therapeutic strategies for the treatment of patients with colon cancer. In the present study, a novel tumor suppressive microRNA, miR-192, was demonstrated to be markedly downregulated in colon cancer cells compared with normal colon cells. By overexpressing miR-192 in colon cancer HCT-116 cells, the results of the present study revealed that miR-192 inhibits cell proliferation, migration and invasion. Bioinformatics were used to determine the target gene of miR-192 and Ras-related protein Rab-2A (RAB2A) was identified as a downstream target of miR-192. Following the determination of the role of the miR-192-RAB2A pathway in colon cancer, small molecules that may regulate miR-192 were screened and the results demonstrated that simvastatin is an activator of miR-192. Furthermore, simvastatin upregulated miR-192 and inhibited the expression of downstream targets of miR-192, which subsequently led to suppressed proliferation, migration and invasion of colon cancer cells. In conclusion, the present study identified a novel colon cancer cell suppressor, as well as a small-molecule activator of the tumor suppressor miR-192, which may represent a therapeutic strategy for the treatment of patients with colon cancer.