title: miR-193a-3p regulates the multi-drug resistance of bladder cancer by targeting the LOXL4 gene and the oxidative stress pathway.
abstract: BACKGROUND
  Chemoresistance is a major obstacle to the curative cancer chemotherapy and presents one of the most formidable challenges in both research and management of cancer.
  
  
  RESULTS
  From the detailed studies of a multi-chemosensitive (5637) versus a chemoresistant (H-bc) bladder cancer cell lines, we showed that miR-193a-3p [GenBank: NR_029710.1] promotes the multi-chemoresistance of bladder cancer cells. We further demonstrated that lysyl oxidase-like 4 (LOXL4) gene [GenBank: NM_032211.6] is a direct target of miR-193a-3p and executes the former's impact on bladder cancer chemoresistance. The Oxidative Stress pathway activity is drastically affected by a forced reversal of miR-193a-3p or LOXL4 levels in cell and may act at the downstream of LOXL4 gene to relay the miR-193a-3p's impact on the multi-chemoresistance in both cultured cells and the tumor xenografts in nude mice.
  
  
  CONCLUSIONS
  In addition to a new mechanistic insight, our results provide a set of the essential genes in this newly identified miR-193a-3p/LOXL4/Oxidative Stress axis as the diagnostic targets for a guided anti-bladder cancer chemotherapy.
authors.forename: Hui
authors.initials: H
authors.lastname: Deng
authors.forename: Lei
authors.initials: L
authors.lastname: Lv
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Meng
authors.forename: Youguang
authors.initials: Y
authors.lastname: Pu
authors.forename: Jun
authors.initials: J
authors.lastname: Xiao
authors.forename: Liting
authors.initials: L
authors.lastname: Qian
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhao
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Daming
authors.initials: D
authors.lastname: Zhang
authors.forename: Yingwei
authors.initials: Y
authors.lastname: Wang
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.forename: Yinghua
authors.initials: Y
authors.lastname: He
authors.affiliation: Cancer Epigenetics Program, Anhui Cancer Hospital, Hefei 230031, Anhui, China. jdzhu0105@vip.163.com.
authors.forename: Jingde
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D017239:Paclitaxel / Q000494:pharmacology; D008249:Protein-Lysine 6-Oxidase; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015203:Reproducibility of Results; D012261:Ribonucleoproteins / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: C546818:MIRN193 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012261:Ribonucleoproteins; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors; D000594:Amino Acid Oxidoreductases; C445682:LOXL4 protein, human; D008249:Protein-Lysine 6-Oxidase; D017239:Paclitaxel