title: Downregulation of histone deacetylase 1 by microRNA-520h contributes to the chemotherapeutic effect of doxorubicin.
abstract: Doxorubicin induces DNA damage to exert its anti-cancer function. Histone deacetylase 1 (HDAC1) can protect the genome from DNA damage. We found that doxorubicin specifically downregulates HDAC1 protein expression and identified HDAC1 as a target of miR-520h, which was upregulated by doxorubicin. Doxorubicin-induced cell death was impaired by exogenous HDAC1 or by miR-520h inhibitor. Moreover, HDAC1 reduced the level of γH2AX by preventing the interaction of doxorubicin with DNA. In summary, doxorubicin downregulates HDAC1 protein expression, by inducing the expression of HDAC1-targeting miR-520h, to exacerbate DNA-doxorubicin interaction. The upregulation of HDAC1 protein may contribute to drug resistance of human cancer cells and targeting HDAC1 is a promising strategy to increase the clinical efficacy of DNA damage-inducing chemotherapeutic drugs.
authors: Department of Medical Oncology, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Qi
authors: Q
authors: Shen
authors: Department of Medical Oncology, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, China.
authors: Qinghua
authors: Q
authors: Yao
authors: Laboratory of Cancer Biology, Institute of Clinical Science, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Jie
authors: J
authors: Sun
authors: Laboratory of Cancer Biology, Institute of Clinical Science, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Lifeng
authors: L
authors: Feng
authors: Department of Medical Oncology, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Haiqi
authors: H
authors: Lu
authors: Laboratory of Cancer Biology, Institute of Clinical Science, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Yanning
authors: Y
authors: Ma
authors: Laboratory of Cancer Biology, Institute of Clinical Science, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Leiming
authors: L
authors: Liu
authors: Department of Medical Oncology, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Faliang
authors: F
authors: Wang
authors: Department of Medical Oncology, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Jiaqiu
authors: J
authors: Li
authors: Laboratory of Cancer Biology, Institute of Clinical Science, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Yongfang
authors: Y
authors: Yue
authors: Laboratory of Cancer Biology, Institute of Clinical Science, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: jinhc@zju.edu.cn.
authors: Hongchuan
authors: H
authors: Jin
authors: Department of Medical Oncology, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: wangxzju@163.com.
authors: Xian
authors: X
authors: Wang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056284:Histone Deacetylase 1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; C575048:MIRN520 microRNA, human; D035683:MicroRNAs; D004317:Doxorubicin; D056284:Histone Deacetylase 1
keywords: Doxorubicin; Drug resistance; Histone deacetylase 1; MicroRNA