LincRNA-p21 activates endoplasmic reticulum stress and inhibits hepatocellular carcinoma

被引：64

作者：

Yang Ning ^{[1
]}

Fu Yong ^{[1
]}

Zhang Haibin ^{[1
]}

Sima Hui ^{[1
]}

Zhu Nan ^{[1
]}

Yang Guangshun ^{[1
]}

机构：

[1] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Hepatobiliary Surg Dept 5, Shanghai, Peoples R China

来源：

ONCOTARGET | 2015年 / 6卷 / 29期

关键词：

lincRNA-p21; hepatocellular carcinoma; ER stress; sorafenib; LONG NONCODING RNA; COLORECTAL-CANCER; SORAFENIB; APOPTOSIS; EXPRESSION; PATHWAY; GENE; CELLS; PROLIFERATION; DISEASE;

D O I：

10.18632/oncotarget.4661

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：28151 / 28163

页数：13

共 33 条

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