Displacement of Bax by BMF Mediates STARD13 3'UTR-Induced Breast Cancer Cells Apoptosis in an miRNA-Depedent Manner

Mol Pharm. 2018 Jan 2;15(1):63-71. doi: 10.1021/acs.molpharmaceut.7b00727. Epub 2017 Dec 7.

Abstract

The balance of pro- and antiapoptotic gene expression programs dominates the apoptotic progress of cancer cells. We previously demonstrated that STARD13 3'UTR suppressed breast cancer metastasis via inhibiting epithelial-mesenchymal transition (EMT). However, the roles of STARD13 3'UTR in breast cancer apoptosis remain elusive. Here, we identified that STARD13 3'UTR promoted cell apoptosis in vitro and in vivo. Mechanistically, STARD13 3'UTR acted as a ceRNA for BMF (Bcl-2 modifying factor), thus increasing BMF expression in an miRNA-dependent manner. Meanwhile, STARD13 3'UTR enhanced the interaction of BMF/Bcl-2 to release Bax (Bcl-2 associated X protein) in breast cancer cells. Finally, we verified the ceRNA relationship between STARD13 and BMF in vivo. Collectively, these findings suggest that STARD13 3'UTR could act as a ceRNA for BMF to promote apoptosis and recognize STARD13 3'UTR as a potential therapeutic target in breast cancer cells.

Keywords: BMF; STARD13; apoptosis; ceRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics*
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Apoptosis / genetics
  • Apoptosis / physiology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Female
  • Flow Cytometry
  • GTPase-Activating Proteins
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Immunoprecipitation
  • In Situ Nick-End Labeling
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • bcl-2-Associated X Protein

Substances

  • 3' Untranslated Regions
  • Adaptor Proteins, Signal Transducing
  • BMF protein, human
  • GTPase-Activating Proteins
  • MicroRNAs
  • STARD13 protein, human
  • Tumor Suppressor Proteins
  • bcl-2-Associated X Protein