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      Long non-coding RNA UCA1 increases chemoresistance of bladder cancer cells by regulating Wnt signaling.

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          Abstract

          Chemotherapy is a reasonable alternative to cystectomy in patients with invasive and advanced bladder cancer. However, bladder cancer cells often develop drug resistance to these therapies, and ~ 50% of patients with advanced bladder cancer do not respond to chemotherapy. Recent studies have shown that long non-coding RNA (lncRNA) is involved in the development of chemoresistance. Here we investigated the role of the urothelial cancer-associated 1 (UCA1) lncRNA in cisplatin resistance during chemotherapy for bladder cancer. We showed that cisplatin-based chemotherapy results in up-regulation of UCA1 expression in patients with bladder cancer. Similarly, UCA1 levels are increased in cisplatin-resistant bladder cancer cells. Over-expression of UCA1 significantly increases the cell viability during cisplatin treatment, whereas UCA1 knockdown reduces the cell viability during cisplatin treatment. UCA1 inhibition also partially overcomes drug resistance in cisplatin-resistant T24 cells. Furthermore, we showed that UCA1 positively regulates expression of wingless-type MMTV integration site family member 6 (Wnt6) in human bladder cancer cell lines. UCA1 and Wnt6 expression is also positively correlated in vivo. Up-regulation of UCA1 activates Wnt signaling in a Wnt6-dependent manner. We finally demonstrate that UCA1 increases the cisplatin resistance of bladder cancer cells by enhancing the expression of Wnt6, and thus represents a potential target to overcome chemoresistance in bladder cancer.

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          Author and article information

          Journal
          FEBS J
          The FEBS journal
          Wiley
          1742-4658
          1742-464X
          Apr 2014
          : 281
          : 7
          Affiliations
          [1 ] Department of Renal Transplantation and Urology, Shanghai First People's Hospital, Shanghai Jiaotong University, China.
          Article
          10.1111/febs.12737
          24495014
          4a447cb3-1bf0-45c4-a888-539891cfec1b
          © 2014 FEBS.
          History

          UCA1,Wnt6,bladder cancer,chemoresistance,cisplatin
          UCA1, Wnt6, bladder cancer, chemoresistance, cisplatin

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