title: MiR-193a-3p promotes the multi-chemoresistance of bladder cancer by targeting the HOXC9 gene.
abstract: Chemoresistance prevents the curative cancer chemotherapy and presents a formidable challenge for both cancer researchers and clinicians. We have previously shown that miR-193a-3p promotes the multi-chemoresistance of bladder cancer cells via repressing its three target genes: SRSF2, PLAU and HIC2. Here, we showed that as a new direct target, the homeobox C9 (HOXC9) gene also executes the promoting effect of miR-193a-3p on the bladder cancer chemoresistance from a systematic study of multi-chemosensitive (5637) and resistant (H-bc) bladder cancer cell lines in both cell culture and tumor-xenograft/nude mice system. Paralleled with the changes in the drug-triggered cell death, the activities of both DNA damage response and oxidative stress pathways were drastically altered by a forced reversal of miR-193a-3p or HOXC9 levels in bladder cancer cells. In addition to a new mechanistic insight, our results provide a set of the essential genes in the miR-193a-3p/HOXC9/DNA damage response/oxidative stress pathway axis as the diagnostic targets for the guided anti-bladder cancer chemotherapy.
authors.affiliation: Cancer Epigenetics Program, Anhui Cancer Hospital, Hefei, Anhui 230031, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lv
authors.affiliation: Department of Biology, School of Life Science, Anhui Medical University, Hefei, Anhui 230031, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Cancer Epigenetics Program, Anhui Cancer Hospital, Hefei, Anhui 230031, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Deng
authors.affiliation: Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Cancer Epigenetics Program, Anhui Cancer Hospital, Hefei, Anhui 230031, China.
authors.forename: Youguang
authors.initials: Y
authors.lastname: Pu
authors.affiliation: Department of Radiotherapy, Anhui Cancer Hospital, Hefei, Anhui 230031, China.
authors.forename: Liting
authors.initials: L
authors.lastname: Qian
authors.affiliation: Department of Urology, Anhui Provincial Hospital, Hefei, Anhui, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Gynecologic Cancer, Anhui Cancer Hospital, Hefei, Anhui 230031, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhao
authors.affiliation: School of Life Science and Technology, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, Heilongjiang 150001, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
authors.forename: Daming
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
authors.forename: Yingwei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Cancer Epigenetics Program, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University, Shanghai 200032, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Cancer Epigenetics Program, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University, Shanghai 200032, China.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: He
authors.affiliation: Cancer Epigenetics Program, Anhui Cancer Hospital, Hefei, Anhui 230031, China; Cancer Epigenetics Program, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University, Shanghai 200032, China. Electronic address: jdzhu0105@vip.163.com.
authors.forename: Jingde
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004249:DNA Damage; D019008:Drug Resistance, Neoplasm; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D018398:Homeodomain Proteins; C522807:Hoxc9 protein, human; C546818:MIRN193 microRNA, human; D035683:MicroRNAs
keywords: Bladder cancer; Chemoresistance; DNA damage response; HOXC9; Oxidative stress; miR-193a-3p