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Gene. 2019 May 7;707:78-85. doi: 10.1016/j.gene.2019.05.015. [Epub ahead of print]

miR-613 inhibits liver cancer stem cell expansion by regulating SOX9 pathway.

Author information

1
Department of General Surgery, Cao County People's Hospital, Heze, Shandong Province 274400, China.
2
Department of Biliary Tract Surgery, Third Affiliated Hospital of Second Military Medical University, Shanghai 200438, China. Electronic address: yangpinghua2008@163.com.
3
Department of Urology Surgery, First Affiliated Hospital of Second Military Medical University, Shanghai 200433, China. Electronic address: drlhy@foxmail.com.
4
Department of Oncology, Cao County People's Hospital, Heze, Shandong Province 274400, China. Electronic address: w18053072282@126.com.

Abstract

Liver cancer stem cells (CSCs) contribute to tumorigenesis, progression, drug resistance and recurrence of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liver CSCs remains unclear. Herein, we observed miR-613 expression was downregulated in both chemoresistant and recurrent HCC patients. A remarkable decrease in miR-613 was detected in CD24 or OV6-positive liver CSCs and CSC-enriched hepatoma spheres. Down-regulation of miR-613 facilitated liver CSCs expansion by promoting the dedifferentiation of hepatoma cells and enhancing the self-renewal of liver CSCs. Mechanistically, bioinformatic and luciferase reporter analysis identified SOX9 as a direct target of miR-613. Overexpression of miR-613 inhibited the expression of SOX9 in HCC cells. Special SOX9 siRNA abolished the discrepancy in liver CSCs proportion and the self-renewal capacity between miR-613 overexpression hepatoma cells and control cells, which further confirmed that SOX9 was required in miR-613-inhibited liver CSCs expansion. Furthermore, hepatoma cells with miR-613 overexpression performed more sensitivity to cisplatin or sorafenib treatment. Conclusion: miR-613 could inhibit HCC cell dedifferentiation and liver CSCs expansion by targeting SOX9 signaling and may prove to be a novel therapeutic target for HCC patients.

KEYWORDS:

Hepatocellular carcinoma; Liver cancer stem cell; SOX9; Sorafenib; miR-613

PMID:
31075412
DOI:
10.1016/j.gene.2019.05.015

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