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Oncotarget. 2016 Jun 28;7(26):39694-39704. doi: 10.18632/oncotarget.9233.

Pinin associates with prognosis of hepatocellular carcinoma through promoting cell proliferation and suppressing glucose deprivation-induced apoptosis.

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Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116027, China.
Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116011, China.


The roles of Pinin have been well studied in epithelial cell-cell adhesion and RNA alternative splicing, which suggests its involvement in cancer progression. However, little is known about the association between Pinin expression and hepatocellular carcinoma (HCC) tumorigenesis. In this study we report increased expression of Pinin in HCC tissues and cells. Elevated levels of Pinin closely associates with pathological grade and overall survival of patients with hepatocellular carcinoma. Suppression of Pinin expression via lentivirus mediated shRNA knockdown inhibits HCC cell proliferation, colony formation, cell viability, but promotes glucose deprivation (GD)-induced cell apoptosis. On the contrary, overexpression of Pinin reverses these effects observed in Pinin depleted cells. Meanwhile, overexpression of Pinin attenuates GD initiated poly ADP-ribose polymerase (PARP) cleavage and ERK1/2 dephosphorylation, which can be completely blocked with MEK1/2 inhibitor U0126. Therefore, we conclude that Pinin contributes to HCC progression and resistance to GD-induced apoptosis via maintaining ERK1/2 activation and hence may be a potential therapeutic target in hepatocellular carcinoma treatment.


ERK; Pinin; apoptosis; hepatocellular carcinoma; proliferation

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