Premium
Downregulation of histone deacetylase 1 by microRNA‐520h contributes to the chemotherapeutic effect of doxorubicin
Author(s) -
Shen Qi,
Yao Qinghua,
Sun Jie,
Feng Lifeng,
Lu Haiqi,
Ma Yanning,
Liu Leiming,
Wang Faliang,
Li Jiaqiu,
Yue Yongfang,
Jin Hongchuan,
Wang Xian
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.11.034
Subject(s) - doxorubicin , hdac1 , downregulation and upregulation , histone deacetylase , cancer research , dna damage , histone deacetylase inhibitor , microrna , histone , chemistry , biology , pharmacology , dna , biochemistry , chemotherapy , gene , genetics
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.