MicroRNA-575 regulates development of gastric cancer by targeting PTEN

Biomed Pharmacother. 2019 May:113:108716. doi: 10.1016/j.biopha.2019.108716. Epub 2019 Mar 4.

Abstract

MicroRNA-575 (miR-575) is oncogene in many tumors. However, the role of miR-575 in the progression of gastric cancer (GC) is still unknown. The aim of this study was to identify whether miR-575 play a role in the development of GC. We obtained GC cell lines, GC tissues from 40 patients to measure the levels of miR-575 and its predicted target PTEN by using RT‑PCR, immunohistochemistry or western blot analysis. MGC-803 cells were transfected with miR-575 inhibitor, and cells viability and apoptosis were measured. miR-575 aberrantly up-regulated in GC tissues and GC cell lines compared with corresponding control. In cell lines, MGC‑803 expressed highest level of miR-575 among the tested cells. The level of miR-575 was correlated with the tumor size, AJCC stage and prognosis, but not with the other clinical parameters. Knockdown of miR-575 inhibited proliferation and promoted apoptotic death of MGC-803 cells both in vitro and vivo. PTEN levels (both mRNA and protein) were remarkably decreased in cancer tissues compared with the paired-adjacent tissues, and negatively correlated with miR-575 in the tissues. By using luciferase reporter assay, we found PTEN was a direct downstream target of miR-575, and negatively regulated by miR-575 via targeting its 3'UTR. Knockdown or overexpression of miR-575 in MGC-803 cells negatively regulated PTEN expression. Finally, silencing PTEN partially impaired anti-proliferative effects of miR-575 inhibitor. miRNA-575 serves a pivotal role in GC as a cancer promoter gene by targeting PTEN to regulate proliferation and apoptosis of the cancer cells.

Keywords: Apoptosis; Gastric cancer; PTEN; Proliferation; microRNA-575.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Cell Survival / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Xenograft Model Antitumor Assays

Substances

  • MIRN575 microRNA, human
  • MicroRNAs
  • PTEN Phosphohydrolase
  • PTEN protein, human