Long non-coding RNA OIP5-AS1 promotes the growth of gastric cancer through the miR-367-3p/HMGA2 axis

Dig Liver Dis. 2020 Jul;52(7):773-779. doi: 10.1016/j.dld.2019.11.017. Epub 2020 Jan 17.

Abstract

Increasing evidence shows that aberrant lncRNAs expression contributes to the progression of gastric cancer (GC). The role of the novel lncRNA OIP5-AS1 and its underlying mechanisms in the growth of GC is largely unknown. Here we demonstrate for the first time that OIP5-AS1 expression was up-regulated in GC tissues and cell lines, which significantly correlated with unfavorable clinical characteristics and shorter survival. The results of in vitro and in vivo gain- and loss-of-function experiments indicate that OIP5-AS1 promoted cell proliferation and colony formation while inhibiting apoptosis of GC cells. OIP5-AS1 functioned as an endogenous sponge for miR-367-3p in GC cells. Restoration of miR-367-3p expression abolished the biological effects of OIP5-AS1 on GC cells. Moreover, we show that HMGA2 was a downstream target of miR-367-3p and mediated the effects of OIP5-AS1 on GC cells. OIP5-AS1 regulated the activities of the PI3K/AKT and Wnt/β-catenin pathways through HMGA2. In conclusion, OIP5-AS1 functions as an oncogenic lncRNA that promotes the progression of GC and may serve as a therapeutic target for managing GC.

Keywords: Gastric cancer; HMGA2; OIP5-AS1; Proliferation; miR-367-3p.

MeSH terms

  • Animals
  • Apoptosis
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • HMGA2 Protein / metabolism*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / metabolism*
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction*
  • Stomach Neoplasms / metabolism*
  • Up-Regulation
  • Xenograft Model Antitumor Assays

Substances

  • HMGA2 Protein
  • HMGA2 protein, human
  • MIRN367 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long noncoding RNA OIP5, human