title: LincRNA-p21 activates endoplasmic reticulum stress and inhibits hepatocellular carcinoma.
abstract: 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.
authors: Hepatobiliary Surgery Department V, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors: Ning
authors: N
authors: Yang
authors: Hepatobiliary Surgery Department V, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors: Yong
authors: Y
authors: Fu
authors: Hepatobiliary Surgery Department V, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors: Haibin
authors: H
authors: Zhang
authors: Hepatobiliary Surgery Department V, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors: Hui
authors: H
authors: Sima
authors: Hepatobiliary Surgery Department V, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors: Nan
authors: N
authors: Zhu
authors: Hepatobiliary Surgery Department V, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors: Guangshun
authors: G
authors: Yang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology; D062085:RNA, Long Noncoding / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077157:Sorafenib; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D062085:RNA, Long Noncoding; D009536:Niacinamide; D000077157:Sorafenib
keywords: ER stress; hepatocellular carcinoma; lincRNA-p21; sorafenib