Back to Search
Start Over
Knockdown of miR-27a sensitizes colorectal cancer stem cells to TRAIL by promoting the formation of Apaf-1-caspase-9 complex
- Source :
- Oncotarget
- Publication Year :
- 2017
- Publisher :
- Impact Journals, LLC, 2017.
-
Abstract
- // Rui Zhang 1 , Jian Xu 1 , Jian Zhao 1 and Jinghui Bai 2 1 Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Insititute, Shenyang 110042, China 2 Department of Internal Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Insititute, Shenyang 110042, China Correspondence to: Jinghui Bai, email: lnjinghuibai@sohu.com 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.
- Subjects :
- 0301 basic medicine
Programmed cell death
Colorectal cancer
colorectal cancer stem cells
TRAIL
Transfection
caspase-9
TNF-Related Apoptosis-Inducing Ligand
03 medical and health sciences
0302 clinical medicine
Cancer stem cell
Cell Line, Tumor
microRNA
medicine
Humans
Gene knockdown
miR-27a
business.industry
Cancer
Oligonucleotides, Antisense
medicine.disease
Caspase 9
MicroRNAs
Apoptotic Protease-Activating Factor 1
030104 developmental biology
Oncology
Gene Knockdown Techniques
030220 oncology & carcinogenesis
Cancer cell
Immunology
Neoplastic Stem Cells
Cancer research
Apaf-1
Stem cell
Colorectal Neoplasms
business
HT29 Cells
Research Paper
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....aa020389a2e1e58115762110a8141465