Downregulation of histone deacetylase 1 by microRNA-520h contributes to the chemotherapeutic effect of doxorubicin |
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Authors: | Qi Shen Qinghua Yao Jie Sun Lifeng Feng Haiqi Lu Yanning Ma Leiming Liu Faliang Wang Jiaqiu Li Yongfang Yue Hongchuan Jin Xian Wang |
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Affiliation: | 1. Department of Medical Oncology, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China;2. Department of Medical Oncology, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, China;3. Laboratory of Cancer Biology, Institute of Clinical Science, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China |
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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. |
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Keywords: | Doxorubicin Histone deacetylase 1 MicroRNA Drug resistance |
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