PTP1B markedly promotes breast cancer progression and is regulated by miR-193a-3p

FEBS J. 2019 Mar;286(6):1136-1153. doi: 10.1111/febs.14724. Epub 2018 Dec 26.

Abstract

The protein tyrosine phosphatase PTP1B, which is encoded by PTPN1, is a ubiquitously expressed nonreceptor protein tyrosine phosphatase. PTP1B has long been known to negatively regulate insulin and leptin receptor signalling. Recently, it was reported to be aberrantly expressed in cancer cells and to function as an important oncogene. In this study, we found that PTP1B protein levels are dramatically increased in breast cancer (BC) tissues and that PTP1B promotes the proliferation, and suppresses the apoptosis, of both HER2-positive and triple-negative BC cell lines. Bioinformatics analysis identified that the miRNA, miR-193a-3p, might potentially target PTP1B. We demonstrate that miR-193a-3p regulates PTP1B in BC cells and that it regulates the proliferation and apoptosis of BC cells by targeting PTP1B, both in vitro and in vivo. In conclusion, this study confirms that PTP1B acts as an oncogene in BC and demonstrates that miR-193a-3p can serve as a tumour suppressor gene in BC by targeting PTP1B.

Keywords: PTP1B; apoptosis; breast cancer; miR-193a-3p; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Proliferation
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Prognosis
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • MIRN193 microRNA, human
  • MicroRNAs
  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1