LincRNA-p21 activates endoplasmic reticulum stress and inhibits hepatocellular carcinoma
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Yang Ning1,*, Fu Yong1,*, Zhang Haibin1, Sima Hui1, Zhu Nan1, Yang Guangshun1
1Hepatobiliary Surgery Department V, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
*These authors have contributed equally to this work
Yang Guangshun, e-mail: [email protected]
Keywords: lincRNA-p21, hepatocellular carcinoma, ER stress, sorafenib
Received: April 18, 2015 Accepted: July 08, 2015 Published: July 20, 2015
LincRNA-p21 is a downstream long non-coding RNA (lncRNA) transcript of p53. LincRNA-p21 serves as a repressor in p53-dependent transcriptional responses and participates in diverse biological processes, including apoptosis, cell cycle, metabolism and pluripotency. However, the role of lincRNA-p21 in human hepatocellular carcinoma remains to be defined. Here in this work, we demonstrated that lincRNA-p21 acted as a tumor suppressive lncRNA in human hepatocellular carcinoma. We firstly found the downregulation of lincRNA-p21 level in human hepatocellular carcinoma tissues, and showed that low expression of lincRNA-p21 was associated with high disease stage and predicted poor survival. Further we showed that lincRNA-p21 knockdown promoted proliferation and colony formation of HepG2, Huh7 and Bel-7042 cells in vitro, while lincRNA-p21 overexpression obtained oppose results. Using tumor xenograft experiments, we also demonstrated that lincRNA-p21 inhibited HepG2 cell growth in vivo and lincRNA-p21 contributed to sorafenib-induced growth regression of HepG2 cell in vivo. Further mechanism analysis revealed that lincRNA-p21 promoted ER stress both in vitro and in vivo, which facilitated apoptosis of hepatocellular carcinoma cells. Finally, we demonstrated that ER stress accounted for lincRNA-p21 effects on apoptosis, proliferation and in vivo growth of hepatocellular carcinoma. These findings implicate that lincRNA-p21 is a potential prognostic factor and therapeutic target for human hepatocellular carcinoma.
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