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

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 (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.