STAT3 is required for MiR-17-5p-mediated sensitization to chemotherapy-induced apoptosis in breast cancer cells

Oncotarget. 2017 Feb 28;8(9):15763-15774. doi: 10.18632/oncotarget.15000.

Abstract

Signal transducer and activator of transcription 3 (STAT3) controls cell survival, growth, migration, and invasion. Here, we observed that STAT3 exerted anti-apoptotic effects in breast cancer cells. On the other hand, miR-17-5p induced apoptosis in breast cancer cells, and overexpression of miR-17-5p sensitized MCF-7 cells to paclitaxel-induced apoptosis via STAT3. Overexpression of STAT3 in MCF-7 cells decreased paclitaxel-induced apoptosis, but STAT3 knockout abolished the miR-17-5p-induced increases in apoptosis. Finally, miR-17-5p promoted apoptosis by increasing p53 expression, which was inhibited by STAT3. These results demonstrate a novel pathway via which miR-17-5p inhibits STAT3 and increases p53 expression to promote apoptosis in breast cancer cells.

Keywords: STAT3; apoptosis; breast cancer; miR-17-5p; paclitaxel.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Blotting, Western
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Estrogen Antagonists / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • Paclitaxel / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor / genetics*
  • STAT3 Transcription Factor / metabolism
  • Tamoxifen / pharmacology
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • 3' Untranslated Regions
  • Antineoplastic Agents, Phytogenic
  • Estrogen Antagonists
  • MIRN17 microRNA, human
  • MicroRNAs
  • STAT3 Transcription Factor
  • Tumor Suppressor Protein p53
  • Tamoxifen
  • Paclitaxel