1. Hepatic stellate cells promote the progression of hepatocellular carcinoma through microRNA-1246-RORα-Wnt/β-Catenin axis.
- Author
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Huang, Jin-Long, Fu, Yi-Peng, Gan, Wei, Liu, Gao, Zhou, Pei-Yun, Zhou, Cheng, Sun, Bao-Ye, Guan, Ruo-Yu, Zhou, Jian, Fan, Jia, Yi, Yong, and Qiu, Shuang-Jian
- Subjects
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LIVER cells , *METASTASIS , *TUMOR growth , *GENE expression , *LIVER cancer - Abstract
Hepatic stellate cells (HSCs) play vital roles in tumorigenesis and progression of hepatocellular carcinoma (HCC). However, there remains a lack of high-throughput studies on gene expression alterations in HCC cells in response to direct interactions with HSCs. In this study, we established a direct co-culture model of HSCs and HCC cells. We found that the expression of a set of miRNAs, most notably miR-1246, was triggered by HSCs. RORα was confirmed as the target gene of miR-1246. Either overexpression of miR-1246 or knockdown of RORα enhanced the proliferation, invasiveness, and metastatic capability of HCC both in vitro and in vivo, through Wnt/β-catenin pathway activation and promotion of epithelial-mesenchymal transition (EMT). Moreover, upregulation of miR-1246 and repression of RORα were prominent features of aggressive clinical HCC. The miR-1246-RORα-Wnt/β-catenin axis is a novel pathway through which HSCs accelerate HCC progression. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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