CYLD downregulates Livin and synergistically improves gemcitabine chemosensitivity and decreases migratory/invasive potential in bladder cancer: the effect is autophagy-associated

Lei Yin, Shuai Liu, Chensheng Li, Sentai Ding, Dongbin Bi, Zhihong Niu, Liping Han, Wenjia Li, Dexuan Gao, Zheng Liu, Jiaju Lu

Although GC (gemcitabine and cisplatin) chemotherapy remains an effective method for treating bladder cancer (BCa), chemoresistance is a major obstacle in chemotherapy. In this study, we determined whether gemcitabine resistance correlates with migratory/invasive potential in BCa and whether this relationship is regulated by the cylindromatosis (CYLD)-Livin module. First, we independently investigated the correlation of CYLD/Livin and gemcitabine resistance with the potential for tumor migration and invasiveness. Second, we found that co-transfected CYLD and Livin dramatically improved sensitivity to gemcitabine chemotherapy and decreased migration/invasion potential. Next, we determined that CYLD may regulate Livin by the NF-κB-dependent pathway. We also found that CYLD overexpression and Livin knockdown might improve gemcitabine chemosensitivity by decreasing autophagy and increasing apoptosis in BCa cells. Finally, the effects of CYLD-Livin on tumor growth in vivo were evaluated. Our study demonstrates that CYLD-Livin might represent a potential therapeutic for chemoresistant BCa.