title: The miR-193a-3p regulated PSEN1 gene suppresses the multi-chemoresistance of bladder cancer.
abstract: Chemoresistance prevents the curative cancer therapy, our understanding of which remains inadequate. Among the differentially expressed genes between the chemosensitive (5637) and chemoresistant (H-bc) bladder cancer cell lines, the expression level of the PSEN1 gene (presenilin 1), a key component of the γ-secretase, is negatively correlated with chemoresistance. A small interfering RNA mediated repression of the PSEN1 gene suppresses cell apoptosis and de-sensitizes 5637 cells, while overexpression of the presenilin 1 sensitizes H-bc cells to the drug-triggered cell death. As a direct target of microRNA-193a-3p that promotes the multi-chemoresistance of the bladder cancer cell, PSEN1 acts as an important executor for the microRNA-193a-3p's positive impact on the multi-chemoresistance of bladder cancer, probably via its activating effect on DNA damage response pathway. In addition to the mechanistic insights, the key players in this microRNA-193a-3p/PSEN1 axis are likely the diagnostic and/or therapeutic targets for an effective chemotherapy of bladder cancer.
authors.affiliation: Cancer Epigenetics Program, Anhui Cancer Hospital, Hefei, Anhui 230031, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Deng
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: 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: Department of Radiotherapy, Anhui Cancer Hospital, Hefei, Anhui 230031, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Meng
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 Urology, Anhui Provincial Hospital, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xiao
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 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: D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D053764:Presenilin-1 / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; C546818:MIRN193 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D012334:RNA, Neoplasm
keywords: Bladder cancer; Chemoresistance; DNA damage response pathway; PSEN1; miR-193a-3p