LINC01018 confers a novel tumor suppressor role in hepatocellular carcinoma through sponging microRNA-182-5p

Am J Physiol Gastrointest Liver Physiol. 2019 Aug 1;317(2):G116-G126. doi: 10.1152/ajpgi.00005.2019. Epub 2019 Apr 25.

Abstract

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality. Emerging evidence has demonstrated that some long noncoding RNAs (lncRNAs) are involved in the development and progression of HCC. Herein, the current study aimed to explore the potential mechanism of LINC01018 in regulating the progression of HCC. Initially, the expression of LINC01018, microRNA-182-5p (miR-182-5p), and forkhead box protein O1 (FOXO1) was quantified in 72 paired HCC and adjacent normal tissue samples as well as HCC cells, followed by identification of the interaction among them. To define the contributory role of LINC01018 in the progression of HCC, the expression of LINC01018, miR-182-5p, or FOXO1 was altered in HCC cells, followed by evaluation of cell proliferation, cell cycle distribution, and cell apoptosis. Finally, in vivo tests were performed to further verify the role of LINC01018 in HCC. It was observed that LINC01018 and FOXO1 were poorly expressed but miR-182-5p was highly expressed in HCC tissues and cells. The upregulation of LINC01018 was shown to decrease proliferation while promoting apoptosis of HCC cells. LINC01018 acted as a sponge of miR-182-5p, which targeted FOXO1. Last, mice injected with Hep3B overexpressing FOXO1 displayed suppressed xenograft tumor formation. Collectively, overexpression of LINC01018 represses proliferation and promotes apoptosis of HCC cells via upregulation of FOXO1 by sponging miR-182-5p, which highlights overexpression of LINC01018 as a candidate suppressor of HCC.NEW & NOTEWORTHY This study provides evidence for understanding the molecular mechanism involved in the progression of hepatocellular carcinoma and identifies a novel network of LINC01018/miR-182-5p/FOXO1. We also conducted in vivo experiments in nude mice to validate the anti-tumor effect of LINC01018.

Keywords: LINC01018; apoptosis; forkhead box protein O1; hepatocellular carcinoma; microRNA-182-5p; proliferation.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Carcinoma, Hepatocellular / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Disease Progression
  • Forkhead Box Protein O1 / genetics*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / genetics*
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • RNA, Long Noncoding / genetics*
  • Up-Regulation

Substances

  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • MicroRNAs
  • Mirn182 microRNA, human
  • RNA, Long Noncoding