title: Long non-coding RNA UCA1 promotes cisplatin/gemcitabine resistance through CREB modulating miR-196a-5p in bladder cancer cells.
abstract: Chemoresistance constitutes the major failing of clinical therapy for bladder cancer. However, the molecular mechanisms involved in the chemoresistance of bladder cancer are unclear. Long non-coding RNAs (lncRNAs) have been implicated in chemotherapeutic drug resistance. Urothelial Cancer Associated 1 (UCA1), an lncRNA, is reportedly upregulated in human bladder carcinoma and promotes cancer cell proliferation, migration, invasion, and drug resistance. In the present study, knockdown of UCA1 decreased chemosensitivity to cisplatin/gemcitabine by suppressing cell proliferation and inducing apoptosis, while overexpression of UCA1 increased chemosensitivity in bladder cancer cells. Moreover, UCA1 activated transcription factor CREB which led to miR-196a-5p expression by binding with its promoter. miR-196a-5p induction is involved in UCA1 inhibition of apoptosis induced by cisplatin/gemcitabine via targeting p27Kip1. These results provide a novel UCA1-CREB-miR-196a-5p paradigm to explain in part how UCA1 functions in cisplatin/gemcitabine resistance, and suggest that UCA1 may be a potential therapeutic target for chemotherapy in bladder cancer.
authors: Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors: Jingjing
authors: J
authors: Pan
authors: Translational Medicine Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors: Xu
authors: X
authors: Li
authors: Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors: Wenjing
authors: W
authors: Wu
authors: Translational Medicine Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors: Mei
authors: M
authors: Xue
authors: Department of Pathology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors: Huilian
authors: H
authors: Hou
authors: Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors: Wen
authors: W
authors: Zhai
authors: Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. Electronic address: chenwei6311@163.com.
authors: Wei
authors: W
authors: Chen
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: C436291:CDKN1B protein, human; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C542543:MIRN196 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; C515159:UCA1 RNA, human; D003841:Deoxycytidine; D050760:Cyclin-Dependent Kinase Inhibitor p27; D002945:Cisplatin; D000093542:Gemcitabine
keywords: Bladder cancer; CREB; Drug resistance; UCA1; miR-196a-5p