title: The miR-193a-3p-regulated ING5 gene activates the DNA damage response pathway and inhibits multi-chemoresistance in bladder cancer.
abstract: As the major barrier to curative cancer chemotherapy, chemoresistance presents a formidable challenge to both cancer researchers and clinicians. We have previously shown that the bladder cancer (BCa) cell line 5637 is significantly more sensitive to the cytoxicity of five chemotherapeutic agents than H-bc cells. Using an RNA-seq-based omic analysis and validation at both the mRNA and protein levels, we found that the inhibitor of growth 5 (ING5) gene was upregulated in 5637 cells compared with H-bc cells, indicating that it has an inhibitory role in BCa chemoresistance. siRNA-mediated inhibition of ING5 increased the chemoresistance and inhibited the DNA damage response pathway in 5637 cells. Conversely, forced expression of EGFP-ING5 decreased the chemoresistance of and activated the DNA damage response pathway in H-bc cells. We also showed that ING5 gene expression is inhibited by miR-193a-3p and is instrumental in miR-193a-3p's role in activating BCa chemoresistance. Our results demonstrate both the role and mechanism of inhibition of BCa chemoresistance by ING5.
authors.affiliation: Department of Biology, School of Life Science, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Cancer Epigenetics Program, Anhui Cancer Hospital, Hefei, Anhui, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Deng
authors.affiliation: Cancer Epigenetics Program, Anhui Cancer Hospital, Hefei, Anhui, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lv
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, 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, 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, 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: Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: Cancer Epigenetics Program, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Cancer Epigenetics Program, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: He
authors.affiliation: Cancer Epigenetics Program, Anhui Cancer Hospital, Hefei, Anhui, China.|Cancer Epigenetics Program, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Jingde
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000107:Acetylation; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D004249:DNA Damage; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D015398:Signal Transduction; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C508131:ING5 protein, human; C546818:MIRN193 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
keywords: ING5; bladder cancer; chemoresistance; miR-193a-3p; protein acetylation