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 approximately 50% of patients with advanced bladder cancer do not respond to chemotherapy. Recent studies show that long-noncoding RNA (lncRNA) is involved in the development of chemoresistance.
Here researchers from the Shanghai Jiaotong University investigated the role of lncRNA-UCA1 in cisplatin resistance during chemotherapy for bladder cancer. They showed that cisplatin-based chemotherapy results in upregulation of UCA1 expression in patients with bladder cancer. Similarly, UCA1 levels are increased in cisplatin-resistant bladder cancer cells. Overexpression of UCA1 significantly increases the cell viability, whereas UCA1 knockdown reduces the cell viability during cisplatin treatment. UCA1 inhibition also partially overcomes drug resistance in cisplatin-resistant T24 cell. Furthermore, they showed that UCA1 positively regulates Wnt6 expression in human bladder cancer cell lines. UCA1 and Wnt6 expression is also positively correlated in vivo. Upregulated UCA1 activates Wnt signaling in a Wnt6-dependent manner. The researchers finally demonstrated that UCA1 increases the cisplatin resistance of bladder cancer cell by enhancing the expression of Wnt6, and thus represents a potential target to overcome chemoresistance in bladder cancer.
- Fan Y, Shen B, Tan M, Mu X, Qin Y, Zhang F, Liu Y. (2014) Long non-coding RNA UCA1 increases chemoresistances of bladder cancer cells by regulating Wnt signaling. FEBS J [Epub ahead of print]. [abstract]