Abstract
Abstract Resistance to fluoropyrimidine based chemotherapy is the major reason for the failure of treating advanced colorectal cancer. The lack of ability for tumor cells to undergo apoptosis after genotoxic stress is the key contributor to such intrinsic mechanism. Mounting evidence has demonstrated that non-coding microRNAs (miRNAs) are crucial regulators of gene expression, in particular, under acute stress. However, there is still very limited knowledge about the role of miRNAs in apoptosis. In this study, we discovered a novel mechanism mediated by miR-129 directly inducing apoptosis by suppressing a key anti-apoptotic protein Bcl-2. Ectopic expression of miR-129 promotes apoptosis, inhibits cell proliferation and causes G2-cell-cycle arrest in colon cancer cells in vitro. The intrinsic apoptotic pathway triggered by miR-129 is activated by cleaving caspase-9 and caspase-3. The expression of miR-129 is very significantly down-regulated in colorectal cancer tissue specimens compared with the paired normal control samples (p<0.00001). More importantly, we demonstrated that miR-129 functions synergistically with 5-fluorouracil (5-FU) in vitro and in vivo to enhance 5-FU cytotoxicity. These results suggest that miR-129 is a major regulator of apoptosis in colorectal cancer. Therefore, miR-129 may be a potential tumor suppressor in colorectal cancer and a novel candidate for developing miR-129 based therapeutic strategies. Citation Format: Mihriban Karaayvaz, Haiyan Zhai, Jingfang Ju. miR-129 is a potential tumor suppressor in colorectal cancer by regulating apoptosis and modulating fluropyrimidine based chemosensitivity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4185. doi:10.1158/1538-7445.AM2013-4185
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