Long noncoding RNA LINC00488 functions as a ceRNA to regulate hepatocellular carcinoma cell growth and angiogenesis through miR-330-5

Dig Liver Dis. 2019 Jul;51(7):1050-1059. doi: 10.1016/j.dld.2019.03.012. Epub 2019 Apr 17.

Abstract

Background: Long non-coding RNAs (lncRNAs) recently have been identified as influential indicators in a variety of malignancies. Hence, the aim of the present study was to identify a functional lncRNA and its associated effects on hepatocellular carcinoma (HCC) in terms of cellular growth and a ngiogenesis.

Methods and results: Microarray-based analysis revealed a possible regulatory mechanism involving LINC00488, microRNA-330-5p (miR-330-5p) and talin-1 (TLN1) in HCC. Targetscan and RNA22 online tools predicted the relationship among LINC00488, miR-330-5p and TLN1, which were further validated by dual luciferase reporter gene assay, RNA pull-down and RIP. To evaluate the effects of LINC00488 and miR-330-5p on the cellular process of HCC, we performed a series of in vitro and in vivo experiments, with the expression of LINC00488, miR-330-5p, and TLN1 altered by delivering plasmids into Hep3B cell line. The obtained results demonstrated that cells with siRNA-mediated depletion of LINC00488 or restoration of miR-330-5p displayed suppressed abilities of in vitro proliferation as well as of in vivo tumor growth and angiogenesis, while in vitro apoptosis was notably induced.

Conclusion: The fundamental findings of the present study collectively propose that lncRNA LINC00488 can competitively sponge miR-330-5p to regulate TLN1 in relation to the cell growth and angiogenesis in HCC.

Keywords: Angiogenesis; Apoptosis; Hepatocellular carcinoma; LINC00488; Long non-coding RNA; Proliferation; Talin-1; microRNA-330-5p.

MeSH terms

  • Apoptosis
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • MicroRNAs / genetics*
  • Neovascularization, Pathologic
  • RNA, Long Noncoding / genetics*
  • RNA, Small Interfering / genetics
  • Talin / genetics

Substances

  • MIRN330 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • TLN1 protein, human
  • Talin