The Long Noncoding RNA, Growth Arrest-Specific 5, Suppresses Gastric Cancer by Downregulating miR-21 Expression

Pharmacology. 2020;105(7-8):434-444. doi: 10.1159/000504674. Epub 2020 Jan 7.

Abstract

Background: Gastric cancer has become the second major cause of cancer death. The aim of the present study was to explore the relationship between miR-21 and the long noncoding RNA growth arrest-specific 5 (GAS5) in gastric cancer and the effect on gastric cancer cells.

Methods: The expression of miR-21 and GAS5 mRNA was analyzed by quantitative real-time-PCR. Overexpression of GAS5 was used to investigate the biological functions of GAS5 in cells. The cell proliferation was detected by cell counting kit-8 assay and the cell migration and invasion were detected by Transwell. Cell apoptosis was evaluated by Annexin V-FITC/PI staining and apoptosis-related proteins were detected by western blot. The mechanism of GAS5 in vivo was evaluated by the tumorigenesis of nude mice, and dual luciferase reporter was used to determine if miR-21 is a GAS5 target. The inhibition of miR-21 and the simultaneous overexpression of GAS5 and miR-21 were further performed, and the above indicators were detected again.

Results: GAS5 was low expression and miR-21 was high expression in gastric cancer tissues and cells. GAS5 overexpression reduced the proliferation, migration, and invasion of gastric cancer cells and increased the apoptosis of gastric cancer cells. The growth rate of GAS5 group slowed down and the volume of tumor decreased. miR-21 is a GAS5 target and GAS5 inhibits the proliferation of gastric cancer cells by targeting miR-21.

Conclusion: Our research shown that overexpression of GAS5 can significantly inhibit the proliferation, migration, invasion and tumor formation of gastric cancer cells, and promote the apoptosis of gastric cancer cells, which may be related to the targeting inhibition of miR-21 expression by GAS5.

Keywords: Gastric cancer; Growth arrest-specific 5; LncRNA; MiR-21.

Publication types

  • Retracted Publication

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • RNA, Long Noncoding / genetics*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism*

Substances

  • GAS5 long non-coding RNA, human
  • MIRN21 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Neoplasm