Tumor Biology

, Volume 37, Issue 5, pp 6589–6598 | Cite as

Promoter-associated endogenous and exogenous small RNAs suppress human bladder cancer cell metastasis by activating p21 CIP1/WAF1 expression

  • Chenghe Wang
  • Qiangqiang Ge
  • Zhong Chen
  • Jia Hu
  • Fan Li
  • Zhangqun Ye
Original Article

Abstract

Accumulating data suggest that micro RNAs (miRNAs) or double-stranded RNAs (dsRNAs) can activate gene expression by targeting promoters. The cyclin-dependent kinase inhibitor p21 CIP1/WAF1 (p21) has also been shown to suppress epithelial-mesenchymal transition (EMT) which plays a crucial role in the early stage of tumor metastases and invasiveness. In a previous study, we have reported that miR-370-5p is low-expressed in bladder cancer (BCa) tissues and cell lines. Here, we identified that miR-370-5p and sequence homology dsRNA (dsP21-555) fully complementary to promoter hold the potent abilities to induce p21 expression. Moreover, transfection of miR-370-5p or dsP21-555 into BCa cells remarkably inverts EMT-associated genes (increases epithelial cell makers E-cadherin and β-catenin, and decreases mesenchymal cell markers ZEB1 and Vimentin) expression mainly via regulating p21 expression. Besides, through manipulating p21, both the candidates can retard BCa cell migration and invasion. In summary, our results provide evidence that both endogenous and exogenous small RNAs may function to induce p21 expression by interacting with the similar promoter region and impede BCa metastasis.

Keywords

p21 Bladder cancer RNA activation Epithelial-mesenchymal transition Micro RNA Double-stranded RNA 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China [grant number 81372759, China]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Compliance with ethical standards

Conflicts of interest

None

Supplementary material

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13277_2015_4571_MOESM2_ESM.docx (14 kb)
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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Chenghe Wang
    • 1
    • 2
  • Qiangqiang Ge
    • 1
  • Zhong Chen
    • 1
  • Jia Hu
    • 1
  • Fan Li
    • 1
  • Zhangqun Ye
    • 1
  1. 1.Department of Urology, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  2. 2.Department of UrologyShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghaiChina

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