Long non‐coding RNA UCA 1 increases chemoresistance of bladder cancer cells by regulating Wnt signaling

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 (lnc RNA ) is involved in the development of chemoresistance. Here we investigated the role of the urothelial cancer‐associated 1 ( UCA 1) lnc RNA in cisplatin resistance during chemotherapy for bladder cancer. We showed that cisplatin‐based chemotherapy results in up‐regulation of UCA 1 expression in patients with bladder cancer. Similarly, UCA 1 levels are increased in cisplatin‐resistant bladder cancer cells. Over‐expression of UCA 1 significantly increases the cell viability during cisplatin treatment, whereas UCA 1 knockdown reduces the cell viability during cisplatin treatment. UCA 1 inhibition also partially overcomes drug resistance in cisplatin‐resistant T24 cells. Furthermore, we showed that UCA 1 positively regulates expression of wingless‐type MMTV integration site family member 6 (Wnt6) in human bladder cancer cell lines. UCA 1 and Wnt6 expression is also positively correlated in vivo . Up‐regulation of UCA 1 activates Wnt signaling in a Wnt6‐dependent manner. We finally demonstrate that UCA 1 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.