OncoTargets and Therapy (2019-01-01)

Long noncoding RNA UCA1 targets miR-582-5p and contributes to the progression and drug resistance of bladder cancer cells through ATG7-mediated autophagy inhibition

  • Wu J,
  • Li W,
  • Ning J,
  • Yu W,
  • Rao T,
  • Cheng F

Journal volume & issue
Vol. Volume 12
pp. 495 – 508

Abstract

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Junfeng Wu,1,* Wei Li,2,* Jinzhuo Ning,1 Weimin Yu,1 Ting Rao,1 Fan Cheng1 1Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; 2Department of Anesthesiology, People’s Hospital of Wuhan University, Wuhan, Hubei, China *These authors contributed equally to this work Background: Rently, the incidence of bladder cancer has been on the rise. Accumulating researches have been conducted to clarify the molecular mechanisms and potential therapeutic targets of bladder cancer. The present study aims to explore the regulatory mechanism of the urothelial carcinoma-associated 1 (UCA1)-miR-582-5p-ATG7 axis in bladder cancer. Methods: Quantitative real-time polymerase chain reaction was used to detect mRNA level. Relative protein expression was detected by western blot. wound healing assay and transwell were used to determine migration and invasion of cells. in addtion, luciferase reporter assay and immunohistochemistry were performed.Results: UCA1 expression was upregulated in bladder cancer tissues and cells, while the depletion of UCA1 by shRNA resulted in the suppression of cell proliferation, invasion, migration, and drug resistance. Further studies demonstrated that UCA1 could directly interact with miR-582-5p, and that there was an inverse correlation between miR-582-5p and UCA1. In addition, we found that ATG7 is a target of miR-582-5p and can be downregulated by either miR-582-5p overexpression or UCA1 knockdown. In particular, the autophagy is reduced when UCA1 shRNA is introduced. Moreover, the in vivo experiment further demonstrated the contribution of UCA1 in bladder cancer including tumor growth, invasion, and migration, and UCA1 knockdown can inhibit the aforementioned activities. Conclusion: These results provided evidence for a novel UCA1 interaction regulatory network in bladder cancer, that is, UCA1-miR-582-5p-ATG7-autophagy axis. Our study provides a new insight into the treatment of bladder cancer. Keywords: lncRNA UCA1, miR-582-5p, bladder cancer, migration and invasion, resistance

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