Abstract 3079: Mechanism of hsa-miR-15a in EMT and chemoresistance in colorectal cancer

Abstract

Abstract Epigenetic alterations such as non-coding microRNAs are critical factors in EMT and chemoresistance. Hsa-miR-15a, as one of the first miRNA identified to be associated with cancer, has been investigated for its role in several types of cancer. We are interested in understanding the molecular and cellular mechanism of hsa-miR-15a in colorectal cancer as hsa-miR-15a is down-regulated in colon cancer and associated with poor patient prognosis. In this study, we have identified several direct key targets of hsa-miR-15a that impact EMT transition, cell cycle and apoptosis. Our results show that the expression of BMI-1, an important regulator of EMT, was suppressed by hsa-miR-15a. The reduction of hsa-miR-15a in colorectal cancer patient samples was significantly inversely correlated with BMI-1 over-expression. Hsa-miR-15a also suppresses the expression of anti-apoptotic protein BCL-2. The suppression of BMI-1, BCL-2 as well as other key targets by hsa-miR-15a has potential for increasing chemosensitivity as well as disrupting cancer stem cell self renewal. In addition, hsa-miR-15a also has potential as a prognostic biomarker in colorectal cancer. This work will provide a further understanding of the mechanism of hsa-miR-15a loss in colorectal cancer and its clinical significance in relationship with its targets and pathways. The functional significance of hsa-miR-15a in regulating key targets and pathways establishes the foundation for hsa-miR-15a as a potential novel therapeutic strategy for treating colorectal cancer. Citation Format: Andrew Fesler, Haiyan Zhai, Jingfang Ju. Mechanism of hsa-miR-15a in EMT and chemoresistance in colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3079. doi:10.1158/1538-7445.AM2015-3079