Decreased long intergenic noncoding RNA P7 predicts unfavorable prognosis and promotes tumor proliferation via the modulation of the STAT1-MAPK pathway in hepatocellular carcinoma
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Sijie Cheng1, Tieling Li2, Cheng Wang2, Keyu Wang3, Chengcai Lai3, Jin Yan1, Hongxia Fan1, Fang Sun1, Zhaohai Wang1, Peirui Zhang1, Linxiang Yu1, Zhixian Hong1, Guanglin Lei1, Baijun Sun1, Yuan Gao1, Zhaohui Xiao1, Xu Ji1, Ruilan Wang1, Jianzhong Wu1, Xiliang Wang2, Shaogeng Zhang1 and Penghui Yang1,3
1Beijing 302 Hospital, Beijing, 100039, China
2Chinese PLA General Hospital, Beijing, 100853, China
3State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China
Penghui Yang, email: [email protected]
Shaogeng Zhang, email: [email protected]
Keywords: HCC; long noncoding RNA; lincRNA P7
Received: May 31, 2017 Accepted: September 08, 2017 Epub: December 08, 2017 Published: November 16, 2018
Hepatocellular carcinoma (HCC) is the most common neoplasm and is a leading cause of cancer-related death. Despite advances in the diagnosis and management of HCC, its prognosis remain unfavorable. Accumulating evidence has shown that long intergenic noncoding RNAs (lincRNAs) play central roles in the development of HCC. In this study, we identified a long intergenic noncoding RNA referred to as lincRNA P7 in HCC and explored its clinical significance and biological functions in HCC. The expression level of lincRNA P7 was significantly aberrantly deceased in HCC cancer tissues and cells lines. Gain- and loss-of-function experiments revealed that overexpression of lincRNA P7 significantly inhibited the proliferation of HCC-derived cancer cells, whereas lincRNA P7 knockdown promoted cell growth. Mechanistically, lincRNA P7 blocked Erk1/2 signaling and repressed activation of the STAT1 pathway. In nude mouse models, we show that overexpression of lincRNA P7 effectively repressed HCC xenograft tumor growth in vivo. Moreover, a clinical investigation demonstrated that down-regulated lincRNA P7 expression correlated with liver cirrhosis, Hepatitis B virus (HBV) infection, clinical stage of the tumor and recurrence. A Kaplan-Meier survival analysis showed that the expression of lincRNA P7 was significantly related to overall survival (P = 0.003) and recurrence-free survival (P = 0.031). Collectively, our findings suggested that the down-regulation of lincRNA P7 predicts poor clinical outcomes for HCC patients and might be a powerful candidate prognostic biomarker and target in HCC.
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