Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and the third leading cause of death in the world. Early diagnosis, early therapy, finding of new biomarkers and specific therapeutic targets are urgent necessities for CRC patients. Previous reports indicated that loss of miR-137 expression, which is a potential tumor suppressor microRNA and always loses its expression in cancer cells, may contribute to the progression of CRC. However, the detailed underlying mechanism is still unclear. Here, we demonstrated that Aurora-A, a centrosomal serine/threonine kinase that plays essential roles in regulating various important events during cell cycle progression, is one of the targets of miR-137. By luciferase reporter assay, Q-PCR, and Western blot analysis, we demonstrated that miR-137 can target Aurora-A and inhibit its expression. Overexpression of miR-137 results in cell apoptosis in colorectal cancer cells. Expression of miR-137 and Aurora-A in colorectal cancer tissues and colon polyps, the pre-lesion colon tissue, is negative correlated. In addition, the down-regulated miR-137 expression in colon polyps is positive correlated with its size. The treatment of cells with methyltransferase inhibitor 5-Azacytidine induces the expression of miR-137. Our results suggest that losses of miR-137 expression may contribute to the early stage neoplasia in CRC progression. The investigation of the regulatory mechanism of miR-137 mediated Aurora-A inhibition may provide a novel therapeutic strategy for CRC.
Citation Format: Yu-Chuan Huang, Liang-Yi Hung. Tumor suppressive miR-137 targets Aurora-A and leads to apoptosis in colorectal cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4344. doi:10.1158/1538-7445.AM2014-4344