MiR-128-3p overexpression sensitizes hepatocellular carcinoma cells to sorafenib induced apoptosis through regulating DJ-1

X.-L. Guo, H.-B. Wang, J.-K. Yong, J. Zhong, Q.-H. Li

Department of Hepatology and Pancreatology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China. LQHarticle@aliyun.com

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• Oncology

OBJECTIVE: DJ-1 expression is elevated in a variety of tumors and is related to the survival of tumor cells under adverse stimuli. DJ-1 3’-untranslated region (3’-UTR) contains the target of miR-128-3p, and the expression of miR-128-3p is decreased in hepatoma cells. Therefore, we speculate and address in this study, that miR-128-3p can regulate DJ-1 expression in hepatocellular carcinoma (HCC) and play an important role in HCC cells survival.

MATERIALS AND METHODS: MiR-128-3p and DJ-1 expression in HCC cell lines were measured using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot analysis. Dual luciferase reporter assay was adopted to confirm the miR-128-3p binding sequences in the 3’-UTR of DJ-1. Sorafenib-induced apoptosis was evaluated by flow cytometry, and the apoptosis-associated proteins were detected by Western blot analysis. Overexpression of miR-128-3p and DJ-1 were achieved via transfection with miR-128-3p mimic and DJ-1 plasmid, respectively.

RESULTS: We revealed that miR-128-3p expression was downregulated, while DJ-1 expression was upregulated in HCC cell lines, and DJ-1 expression can be regulated by miR-128-3p via directly binding to it. Moreover, functional assays showed that overexpression of miR-128-3p sensitized HCC cells to sorafenib-induced apoptosis, and this phenomenon was partly abolished by DJ-1. Mechanistically, PTEN/PI3K/Akt signaling pathway was found to participate in the miR-128-3p induced sensitivity to sorafenib via DJ-1.

CONCLUSIONS: We conclude that miR-128-3p overexpression sensitized HCC to sorafenib-induced apoptosis via PTEN/PI3K/Akt signaling pathway by regulating DJ-1 expression.

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