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.Cisplatin treatment results in the UCA1 expression in vitro and in vivo. UCA1 overexpression significantly increases the cell viability, whereas UCA1 knockdown reduces the cell viability during cisplatin treatment. UCA1 positively regulates Wnt6 expression in vitro and in vivo. Finally, we demonstrated that UCA1 increases the cisplatin resistance of bladder cancer cell by enhancing the expression of Wnt6.

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