Long non-coding RNA LINC00152 promotes gallbladder cancer metastasis and epithelial-mesenchymal transition by regulating HIF-1α via miR-138

Open Biol. 2017 Jan;7(1):160247. doi: 10.1098/rsob.160247.

Abstract

Long non-coding RNA LINC00152 had been reported as an oncogene in gastric and hepatocellular cancer. In this study, we show that LINC00152 is overexpressed in gallbladder cancer (GBC) tissue samples and cell lines. The high LINC00152 levels correlated negatively with the overall survival time in GBC patients. Functionally, LINC00152 dramatically promoted cell migration, invasion and epithelial-mesenchymal transition (EMT) progression in vitro. In vivo, LINC00152 overexpression significantly promoted tumour peritoneal spreading and metastasis. Mechanistic analyses indicated that LINC00152 functions as a molecular sponge for miR-138, which directly suppresses the expression of hypoxia inducible factor-1α (HIF-1α). We revealed that miR-138 is a suppressor of GBC cell metastasis and EMT progression, and a similar phenomenon was observed in HIF-1α knockdown NOZ cells. Through binding to miR-138, LINC00152 has an oncogenic effect on GBC. Overall, our study suggested that the LINC00152/miR-138/HIF-1α pathway potentiates the progression of GBC, and LINC00152 may be a novel therapeutic target.

Keywords: HIF-1α; epithelial–mesenchymal transition; gallbladder cancer; long non-coding RNA LINC00152; metastasis; miR-138.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition
  • Female
  • Gallbladder Neoplasms / genetics*
  • Gallbladder Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Transplantation
  • Peritoneal Neoplasms / genetics
  • Peritoneal Neoplasms / pathology
  • Peritoneal Neoplasms / secondary*
  • RNA, Long Noncoding / genetics*
  • Survival Analysis
  • Up-Regulation*

Substances

  • 3' Untranslated Regions
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MIRN138 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long non-coding RNA Linc00152, human