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25 November 2018 : Laboratory Research

Long Stress Induced Non-Coding Transcripts 5 (LSINCT5) Promotes Hepatocellular Carcinoma Progression Through Interaction with High-Mobility Group AT-hook 2 and MiR-4516

Ou Li1ABCDE, Zhizhen Li2ABEF, Qinghe Tang3BCD, Yesheng Li4BCD, Shengxian Yuan5BCD, Yang Shen2BCF, Zhenhua Zhang6BDF, Nianfeng Li7ADEF*, Kaijian Chu2ADE, Guanglin Lei8ADEF

DOI: 10.12659/MSM.911179

Med Sci Monit 2018; 24: LBR8510-8523

Abstract

BACKGROUND: Long non-coding RNAs (lncRNAs) have been implicated in various human cancer types. However, the underlying mechanisms involved in hepatocellular carcinoma (HCC) progression remain poorly understood.

MATERIAL AND METHODS: In this study, lncRNA array was used to identify HCC related lncRNAs. RNA immunoprecipitation (RIP) followed mass spectrometry was used to explore lncRNA binding proteins. Western blot, quantitative PCR, tumor sphere formation, migration and viability assay were performed to evaluate the oncogenic role of lncRNAs.

RESULTS: We identified a novel lncRNA named long stress induced non-coding transcripts 5 (LSINCT5) which facilitates HCC progression. LSINCT5 was significantly upregulated in both HCC specimens and cell lines and correlates with poor survival. In vitro experiments showed that LSINCT5 promoted migration and viability of HepG2 and Huh7 cells. The in vivo xenograft mouse model also confirmed an oncogenic role for LSINCT5. RIP in combination with mass spectrometry identified HMGA2 as the LSINCT5 binding partner. LSINCT5 could bind to HMGA2 and decrease proteasome-mediated HMGA2 degradation leading to EMT activation. LSINCT5 also served as a competing endogenous RNA (ceRNA) for miR-4516, resulting in increased STAT3/BclxL expression and attenuated apoptosis.

CONCLUSIONS: Our data have collectively established a lncRNA LSINCT5 mediated process during HCC carcinogenesis and might have provided novel insight into therapeutic targeting.

Keywords: HMGA2 Protein

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750