Department of Biochemistry & Molecular Biology, China Medical University, Shenyang 110026, China; Key Laboratory of Cell Biology, Ministry of Public Health, China Medical University, Shenyang 110026, China; Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110026, China.
Department of Gynecology & Obstetrics, Sheng Jing Hospital, China Medical University, Shenyang 110005, China.
Biochim Biophys Acta Mol Cell Res. 2017 Oct;1864(10):1668-1678. doi: 10.1016/j.bbamcr.2017.06.004. Epub 2017 Jun 15.
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.
Bcl-2 相关抗凋亡基因 3（BAG3）含有一个模块化结构，通过该结构，BAG3 与多种蛋白质相互作用，从而使其具有调节多方面生物过程的能力。BAG3 在许多癌症中常常高度表达并作为一种促生存因子发挥作用。然而，BAG3 的致癌潜力仍不完全清楚。细胞周期调节剂 S 期激酶相关蛋白 2（Skp2）在各种癌症中增加，并在肿瘤发生中发挥重要作用。本研究表明，BAG3 通过上调 Skp2 促进卵巢癌细胞的增殖。BAG3 通过其 3'非翻译区（UTR）稳定 Skp2 mRNA。本研究表明，BAG3 与 Skp2 mRNA 相互作用。此外，miR-21-5p 抑制 Skp2 的表达，而强制表达 BAG3 则会削弱这种抑制作用。这些结果表明，BAG3 的至少一些致癌功能是通过拮抗 miR-21-5p 在卵巢癌细胞中的抑制作用，从而对 Skp2 进行转录后调节来介导的。
