MiR-19b suppresses PTPRG to promote breast tumorigenesis

Oncotarget. 2016 Sep 27;7(39):64100-64108. doi: 10.18632/oncotarget.11799.

Abstract

Protein tyrosine phosphatase receptor type G (PTPRG) is an important tumor suppressor gene in multiple human cancers. In this study, we found that PTPRG protein levels were downregulated in breast cancer tissues while the mRNA levels varied irregularly, implying a post-transcriptional mechanism was involved. Because microRNAs are powerful post-transcriptional regulators of gene expression, we used bioinformatics analysis to search for microRNAs that potentially targets PTPRG in the setting of breast cancer. We identified two specific binding sites for miR-19b in the 3'-untranslated region of PTPRG. We further identified an inverse correlation between miR-19b and PTPRG protein levels, but not mRNA levels, in human breast cancer tissues. By overexpressing or knocking down miR-19b in MCF-7 cells and MDA-231 cells, we experimentally confirmed that miR-19b directly suppresses PTPRG expression. Furthermore, we determined that the inhibition of PTPRG by miR-19b leads to increased proliferation, stimulated cell migration and reduced apoptosis. Taken together, our findings provide the first evidence that miR-19b inhibits PTPRG expression to promote tumorigenesis in human breast cancer.

Keywords: PTPRG; apoptosis; miR-19b; migration; proliferation.

MeSH terms

  • 3' Untranslated Regions
  • Apoptosis
  • Binding Sites
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation / genetics
  • Cell Survival
  • Cell Transformation, Neoplastic / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5 / genetics
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5 / metabolism*

Substances

  • 3' Untranslated Regions
  • MIRN19 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • RNA, Small Interfering
  • PTPRG protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5