Oncotarget

Research Papers:

Maintenance of cancer stemness by miR-196b-5p contributes to chemoresistance of colorectal cancer cells via activating STAT3 signaling pathway

Dong Ren, Bihua Lin, Xin Zhang, Yao Peng, Ziyu Ye, Yan Ma, Yangfang Liang, Longbin Cao, Xiangyong Li, Ronggang Li, Lixia Sun, Qiongru Liu, Jinhua Wu, Keyuan Zhou and Jincheng Zeng _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:49807-49823. https://doi.org/10.18632/oncotarget.17971

Metrics: PDF 2178 views  |   HTML 1965 views  |   ?  


Abstract

Dong Ren1,2,*, Bihua Lin1,*, Xin Zhang1,3, Yao Peng4, Ziyu Ye1, Yan Ma1, Yangfang Liang5, Longbin Cao4, Xiangyong Li1, Ronggang Li3, Lixia Sun3, Qiongru Liu3, Jinhua Wu6, Keyuan Zhou1 and Jincheng Zeng1

1Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Key Laboratory of Medical Bioactive Molecular Research for Department of Education of Guangdong Province, Guangdong Medical University, Dongguan, Guangdong Province, 523808, China

2Department of Orthopedic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, 510080, China

3Department of Pathology, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-Sen University, Jiangmen, Guangdong Province, 529030, China

4Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, 510080, China

5Department of Pathology, Dongguan Hospital Affiliated to Medical College of Jinan University, The Fifth People’s Hospital of Dongguan, Dongguan, Guangdong Province, 523905, China

6Department of Clinical Laboratory, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-Sen University, Jiangmen, Guangdong Province, 529030, China

*These authors contributed equally to this work

Correspondence to:

Jincheng Zeng, email: zengjc@gdmu.edu.cn

Keywords: miR-196b-5p, cancer stem cell, chemotherapeutic resistance, STAT3 signaling pathway, CRC

Received: October 27, 2016     Accepted: May 04, 2017     Published: May 18, 2017

ABSTRACT

Emerging studies indicated that cancer stem cells represent a subpopulation of cells within the tumor that is responsible for chemotherapeutic resistance. However, the underlying mechanism is still not clarified yet. Here we report that miR-196b-5p is dramatically upregulated in CRC tissues and high expression of miR-196b-5p correlates with poor survival in CRC patients. Moreover, recurrent gains (amplification) contribute to the miR-196b-5p overexpression in CRC tissues. Silencing miR-196b-5p suppresses spheroids formation ability, the fraction of SP cells, expression of stem cell factors and the mitochondrial potential, and enhances the apoptosis induced by 5-fluorouracil in CRC cells; while ectopic expression of miR-196b-5p yields an opposite effect. In addition, downregulation of miR-196b-5p resensitizes CRC cells to 5-fluorouracil in vivo. Our results further demonstrate that miR-196b-5p promotes stemness and chemoresistance of CRC cells to 5-fluorouracil via targeting negative regulators SOCS1 and SOCS3 of STAT3 signaling pathway, giving rise to activation of STAT3 signaling. Interestingly, miR-196b-5p is highly enriched in the serum exosomes of patients with CRC compared to the healthy control subjects. Thus, our results unravel a novel mechanism of miR-196b-5p implicating in the maintenance of stem cell property and chemotherapeutic resistance in CRC, offering a potential rational registry of anti-miR-196b-5p combining with conventional chemotherapy against CRC.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 17971