Long noncoding RNA LINC00629 restrains the progression of gastric cancer by upregulating AQP4 through competitively binding to miR-196b-5p

J Cell Physiol. 2020 Mar;235(3):2973-2985. doi: 10.1002/jcp.29203. Epub 2019 Oct 31.

Abstract

Gastric cancer continues to be a common cancer in the world with high incidence and mortality. Accumulating evidence has implicated long noncoding RNAs (lncRNAs) in gastric cancer progression. Here, this study identified the potential role of a novel lncRNA, LINC00629 in gastric cancer and to elucidate the underlying mechanism. Initially, microarray-based gene expression profiling of gastric cancer was employed to identify differentially expressed genes. Next, the expression of LINC00629, microRNA-196b-5p (miR-196b-5p) and aquaporin 4 (AQP4) in clinical gastric cancer tissues was determined and the cell line presenting with the lowest LINC00629 expression was selected. The interaction among LINC00629, miR-196b-5p, and AQP4 was identified. Expression of LINC00629, miR-196b-5p, and AQP4 in gastric cancer cells were altered and then biological behaviors of gastric cancer cells were assessed by 5-ethynyl-2'-deoxyuridine and Transwell assays. Tumor formation in vivo was evaluated in nude mice. In gastric cancer, expression of LINC00629 and AQP4 was downregulated, and expression of miR-196b-5p was upregulated. Proliferation, invasion, and migration of gastric cancer cells were reduced after overexpression of LINC00629. LINC00629 competitively bound to miR-196b-5p, while AQP4 was a target of miR-196b-5p. Either downregulating miR-196b-5p or upregulating AQP4 could restrain the development of gastric cancer in vitro. LINC00629 overexpression repressed the growth of transplanted tumors in vivo. Taken together, LINC00629 competitively bound to miR-196b-5p to upregulate AQP4 expression, thereby inhibiting gastric cancer progression. Therefore, understanding of this mechanism may help to improve gastric cancer treatment.

Keywords: aquaporin 4; gastric cancer; invasion; long noncoding RNA LINC00629; microRNA-196-5p; migration.

MeSH terms

  • Animals
  • Aquaporin 4 / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice, Nude
  • MicroRNAs / genetics*
  • RNA, Long Noncoding / genetics*
  • Stomach Neoplasms / genetics*
  • Up-Regulation

Substances

  • AQP4 protein, human
  • Aquaporin 4
  • MIRN196 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long non-coding RNA LINC00629, human