期刊
CANCER LETTERS
卷 423, 期 -, 页码 113-126出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2017.11.031
关键词
miR-589-5p; Cancer stem cell; Chemotherapeutic resistance; STAT3 signaling pathway; Hepatocellular carcinoma
类别
资金
- Natural Science Foundation of China [81300421, 81602701]
- Natural Science Foundation of Guangdong Province [S2013040014343, 2014A030313090]
- Science and Technology Projects Foundation of Guangdong Province [2016A020215053]
- Doctoral Fund of Ministry of Education of China [20130171120054]
The strength and duration of STAT3 signaling are tightly controlled by multiple negative feedback mechanisms under physical conditions. However, how these serial feedback loops are simultaneously disrupted in cancers, leading to constitutive activation of STAT3 signaling in hepatocellular carcinoma (HCC), remains obscure. Here we report that miR-589-5p is elevated in HCC tissues, which is caused by recurrent gains. Overexpression of miR-589-5p correlates with poor overall and relapse-free survival in HCC patients. Upregulating miR-589-5p enhances spheroid formation ability, fraction of CD133 positive and side population cells, expression of cancer stem cell factors and the mitochondrial potential, and represses the apoptosis induced by doxorubicin in vitro and tumorigenicity in vivo in HCC cells; conversely, silencing miR-589-5p yields an opposite effect. Our findings further demonstrate miR-589-5p promotes the cancer stem cell characteristics and chemoresistance via targeting multiple negative regulators of STAT3 signaling pathway, including SOCS2, SOCS5, PTPN1 and PTPN11, leading to constitutive activation of STAT3 signaling. Collectively, our results unravel a novel mechanism by which miR-589-5p promotes the maintenance of sternness and chemoresistance in HCC, providing a potential rational registry of anti-miR-589-5p combining with conventional chemotherapy against HCC. (C) 2017 Elsevier B.V. All rights reserved.
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