Downregulation of histone deacetylase 1 by microRNA‐520h contributes to the chemotherapeutic effect of doxorubicin. Issue 1 (6th December 2013) - Shen, Qi
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. Abstract : Doxorubicin induces the down‐expression of HDAC1 to exacerbate DNA damage. Doxorubicin specifically downregulate the expression of HDAC1 but not other HDACs. HDAC1 is a target of miR‐520h which was upregulated after doxorubicin treatment. The effect of doxorubicin was impaired by exogenous HDAC1 or miR‐520h inhibitors. HDAC1 reduced γH2AX by interfering the interaction of doxorubicin with genomic DNA.