CYLD downregulates Livin and synergistically improves gemcitabine chemosensitivity and decreases migratory/invasive potential in bladder cancer: the effect is autophagy-associated
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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.
KeywordsGemcitabine Cylindromatosis (CYLD) Livin Bladder cancer (BCa) Autophagy
This work was supported by the Shandong Key Research and Development Project (No. 2015GSF118055 ), Medicine and Healthcare Technology Development Project of Shandong Province (No. 2014WS0341), and Natural Science Foundation of Shandong Province (No. 2014ZRB14513 and 2014ZRB14081).
Compliance with ethical standards
The study had obtained approval from the Committee on Animal Research of Shandong Provincial Hospital of Shandong University, and our care was in accordance with institutional guidelines.
Conflicts of interest
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