Research Papers:
Knockdown of miR27a sensitizes colorectal cancer stem cells to TRAIL by promoting the formation of Apaf1caspase9 complex
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Rui Zhang1, Jian Xu1, Jian Zhao1 and Jinghui Bai2
1Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Insititute, Shenyang 110042, China
2Department of Internal Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Insititute, Shenyang 110042, China
Correspondence to:
Jinghui Bai, email: [email protected]
Keywords: colorectal cancer stem cells, miR-27a, TRAIL, Apaf-1, caspase-9
Received: March 06, 2017 Accepted: March 22, 2017 Published: April 01, 2017
ABSTRACT
MicroRNAs have been proved to participate in multiple biological processes in cancers. For developing resistance to cytotoxic drug, cancer cells, especially the cancer stem cells, usually change their microRNA expression profile to survive in hostile environments. In the present study, we found that expression of microRNA-27a was increased in colorectal cancer stem cells. High level of microRNA-27a was indicated to induce the resistance to TNF-related apoptosis-inducing ligand (TRAIL). Knockdown of microRNA-27a resensitized colorectal cancer stem cells to TRAIL-induced cell death. Mechanically, the gene of Apaf-1, which is associated with the mitochondrial apoptosis, was demonstrated to be the target of microRNA-27a in colorectal cancer stem cells. Knockdown of microRNA-27a increased the expression level of Apaf-1, thus enhancing the formation of Apaf-1-caspase-9 complex and subsequently promoting the TRAIL-induced apoptosis in colorectal cancer stem cells. These findings suggested that knockdown of microRNA-27a in colorectal cancer stem cells by the specific antioligonucleotides was potential to reverse the chemoresistance to TRAIL. It may represent a novel therapeutic strategy for treating the colorectal cancer more effectively.