Long non-coding RNA UCA1 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 (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.
Department of Renal Transplantation and Urology, Shanghai First People's Hospital, Shanghai Jiaotong University, China.
Yu
Y
Fan
Bing
B
Shen
Mingyue
M
Tan
Xinyu
X
Mu
Yan
Y
Qin
Fang
F
Zhang
Yong
Y
Liu
D000368:Aged; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008875:Middle Aged; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway
D062085:RNA, Long Noncoding; C515159:UCA1 RNA, human; C490674:WNT6 protein, human; D051153:Wnt Proteins; D002945:Cisplatin
UCA1; Wnt6; bladder cancer; chemoresistance; cisplatin