RhoGDIβ promotes Sp1/MMP‐2 expression and bladder cancer invasion through perturbing miR‐200c‐targeted JNK2 protein translation. Issue 11 (11th September 2017)

• Record Type: Journal Article
• Authors: Huang, Haishan; Jin, Honglei; Zhao, Huirong; Wang, Jingjing; Li, Xin; Yan, Huiying; Wang, Shuai; Guo, Xirui; Xue, Lei; Li, Jingxia; Peng, Minggang; Wang, Annette; Zhu, Junlan; Wu, Xue‐Ru; Chen, Changyan; Huang, Chuanshu
• Is Part Of: Molecular oncology. Volume 11:Issue 11(2017)
• Page Start: 1579
• Page End: 1594
• Publication Date: 2017-09-11
• Subjects: bladder cancer -- invasion -- miR‐200c -- RhoGDIβ; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1002/1878-0261.12132
• Languages: English
• ISSNs: 1574-7891

Abstract

Abstract : Our most recent studies demonstrate that RhoGDIβ is able to promote human bladder cancer (BC) invasion and metastasis in an X‐link inhibitor of apoptosis protein‐dependent fashion accompanied by increased levels of matrix metalloproteinase (MMP)‐2 protein expression. We also found that RhoGDIβ and MMP‐2 protein expressions are consistently upregulated in both invasive BC tissues and cell lines. In the present study, we show that knockdown of RhoGDIβ inhibited MMP‐2 protein expression accompanied by a reduction of invasion in human BC cells, whereas ectopic expression of RhoGDIβ upregulated MMP‐2 protein expression and promoted invasion as well. The mechanistic studies indicated that MMP‐2 was upregulated by RhoGDIβ at the transcriptional level by increased specific binding of the transcription factor Sp1 to the mmp‐2 promoter region. Further investigation revealed that RhoGDIβ overexpression led to downregulation of miR‐200c, whereas miR‐200c was able directly to target 3′‐UTR of jnk2 mRNA and attenuated JNK2 protein translation, which resulted in attenuation of Sp1 mRNA and protein expression in turn, inhibiting Sp1‐dependent mmp‐2 transcription. Collectively, our studies demonstrate that RhoGDIβ overexpression inhibits miR‐200c abundance, which consequently results in increases of JNK2 protein translation, Sp1 expression, mmp‐2 transcription, and BC invasion. These findings, together with our previous results showing X‐link inhibitor of apoptosis protein mediating mRNA stabilization of both RhoGDIβ and mmp‐2, reveal the nature of the MMP‐2 regulatory network, which leads to MMP‐2 overexpression and BC invasion. Abstract : Our studies demonstrate that RhoGDIβ overexpression inhibits miR‐200c abundance, which consequently results in increases of JNK2 protein translation, Sp1 expression, MMP‐2 transcription, and bladder cancer invasion. These findings, together with our previous results showing XIAP mediating mRNA stabilization of both RhoGDIβ and MMP‐2, reveal the nature of MMP‐2 regulatory network, which leads to MMP‐2 overexpression and bladder cancer invasion.