BAG3 promotes proliferation of ovarian cancer cells via post-transcriptional regulation of Skp2 expression

Biochim Biophys Acta Mol Cell Res. 2017 Oct;1864(10):1668-1678. doi: 10.1016/j.bbamcr.2017.06.004. Epub 2017 Jun 15.

Abstract

Bcl-2 associated athanogene 3 (BAG3) contains a modular structure, through which BAG3 interacts with a wide range of proteins, thereby affording its capacity to regulate multifaceted biological processes. BAG3 is often highly expressed and functions as a pro-survival factor in many cancers. However, the oncogenic potential of BAG3 remains not fully understood. The cell cycle regulator, S-phase kinase associated protein 2 (Skp2) is increased in various cancers and plays an important role in tumorigenesis. The current study demonstrated that BAG3 promoted proliferation of ovarian cancer cells via upregulation of Skp2. BAG3 stabilized Skp2 mRNA via its 3'-untranslated region (UTR). The current study demonstrated that BAG3 interacted with Skp2 mRNA. In addition, miR-21-5p suppressed Skp2 expression, which was compromised by forced BAG3 expression. These results indicated that at least some oncogenic functions of BAG3 were mediated through posttranscriptional regulation of Skp2 via antagonizing suppressive action of miR-21-5p in ovarian cancer cells.

Keywords: BAG3; Ovarian cancer cells; Skp2; miR-21-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Animals
  • Apoptosis Regulatory Proteins / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • RNA Processing, Post-Transcriptional / genetics
  • RNA, Messenger / genetics
  • S-Phase Kinase-Associated Proteins / genetics*
  • Xenograft Model Antitumor Assays

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • BAG3 protein, human
  • MIRN21 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • S-Phase Kinase-Associated Proteins