Maintenance of Cancer Stemness by MiR-196b-5p Contributes to Chemoresistance of Colorectal Cancer Cells Via Activating STAT3 Signaling Pathway

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Jun 8

PMID 28591704

Citations 101

Authors

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

Jincheng Zeng

Affiliations

Soon will be listed here.

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.

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