microRNA-19a-3p promotes tumor metastasis and chemoresistance through the PTEN/Akt pathway in hepatocellular carcinoma - 11/07/18

Doi : 10.1016/j.biopha.2018.06.097

Xue-Mei Jiang ^a,^b,^{^{1
These authors contributed equally to this work.}}, Xiang-Nan Yu ^a,^{^{1
These authors contributed equally to this work.}}, Tao-Tao Liu ^a, Hai-Rong Zhu ^a, Xuan Shi ^a, Enkhnaran Bilegsaikhan ^a, Hong-Ying Guo ^a, Guang-Qi Song ^a, Shu-Qiang Weng ^a, Xiao-Xi Huang ^b, Ling Dong ^a, Harry L.A. Janssen ^c, Xi-Zhong Shen ^a,^d,^e, Ji-Min Zhu ^a,^⁎
^a Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China
^b Department of Gastroenterology, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, Haikou, China
^c Division of Gastroenterology, University of Toronto & University Health Network, Toronto, Canada
^d Shanghai Institute of Liver Disease, Shanghai, China
^e Key Laboratory of Medical Molecular Virology, Shanghai Medical College of Fudan University, Shanghai, China

^⁎Corresponding author at: Department of Gastroenterology, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai 200032, China.Department of GastroenterologyZhongshan Hospital of Fudan University180 Fenglin Rd.Shanghai200032China

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Abstract

microRNA-19a-3p (miR-19a-3p) has been reported to regulate cell proliferation in hepatocellular carcinoma (HCC), but its role in HCC metastasis remains unknown. In this study, miR-19a-3p was noted to be upregulated in HCC specimens and cell lines. Aberrant expression of miR-19a-3p stimulated HCC cell metastasis, and phosphatase and tensin homolog (PTEN) was shown to be a direct target of miR-19a-3p. miR-19a-3p-mediated HCC metastasis was reversed by restoration of PTEN or could be imitated by silencing of PTEN. Modulation of miR-19a-3p also altered expression of phosphorylated Akt, a downstream mediator of PTEN. Moreover, aberrant expression of miR-19a-3p induced sorafenib resistance by regulating the PTEN/Akt pathway. In conclusion, ectopic expression of miR-19a-3p contributes to HCC metastasis and chemoresistance by modulating PTEN expression and the PTEN-dependent pathways.

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Keywords : microRNA-19a-3p, Hepatocellular carcinoma, Metastasis, Chemoresistance

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Vol 105

P. 1147-1154 - septembre 2018 Retour au numéro

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microRNA-19a-3p promotes tumor metastasis and chemoresistance through the PTEN/Akt pathway in hepatocellular carcinoma - 11/07/18

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