miR-146b Regulates Cell Proliferation and Apoptosis in Gastric Cancer by Targeting PTP1B

Dig Dis Sci. 2020 Feb;65(2):457-463. doi: 10.1007/s10620-019-05771-8. Epub 2019 Aug 22.

Abstract

Background/aims: The purpose of this study is to explore the inhibition or activation effects of microRNA-146 B on the expression of PTP1B in gastric cancer cells.

Methods: The expressions of PTP1B and miR-146b in gastric cancer were detected by RT-qPCR. The effects of miR-146b on cell apoptosis and proliferation of gastric cancer were detected. The methods used in the detection process included Annexin V/PI dying method, colony formation assay, and MTT assay. The downstream target gene miR-146b was predicted and screened by bioinformatics and luciferase reporter assay. The mRNA and protein expressions of the target gene PTP1B miR-146b were determined using RT-qPCR and western blot. The expression of miR-146 B in mice was detected by the cells transfected with microRNA-146 B in vivo.

Results: Compared with normal tissues, PTP1B was higher and miR-146b was lower in cancer cells. Over-expression of miR-146b can inhibit cell viability and increase the apoptosis rate. According to the luciferase reporter assay, PTP1B was the downstream target gene of miR-146b. The re-introduction of PTP1B reversed the growth inhibition and apoptosis of gastric cancer cells induced by miR-146b. From the mouse xenograft model, the over-expression of miR-146b inhibited the tumor growth and reduced the expression level of PTP1B.

Conclusion: miR-146b directly inhibits the expression of PTP1B and suppressed the growth and development of gastric cancer.

Keywords: Apoptosis; Gastric cancer; PTP1B; Proliferation; miR-146b.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Transplantation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / genetics*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology

Substances

  • MIRN146 microRNA, human
  • MicroRNAs
  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1