Downregulation of histone deacetylase 1 by microRNA‐520h contributes to the chemotherapeutic effect of doxorubicin
Downregulation of histone deacetylase 1 by microRNA‐520h contributes to the chemotherapeutic effect of doxorubicin
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DOI：
10.1016/j.febslet.2013.11.034
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发表时间：
2014-01
期刊：
影响因子：
3.5
通讯作者：
Q. Shen;Qinghua Yao;Jie Sun;Lifeng Feng;Haiqi Lu;Yanning Ma;Leiming Liu;Faliang Wang;Jiaqiu Li;Yongfang Yue;Hongchuan Jin;Xian Wang
中科院分区：
文献类型：
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作者：
Q. Shen;Qinghua Yao;Jie Sun;Lifeng Feng;Haiqi Lu;Yanning Ma;Leiming Liu;Faliang Wang;Jiaqiu Li;Yongfang Yue;Hongchuan Jin;Xian Wang
阿霉素通过诱导 DNA 损伤来发挥其抗癌功能。组蛋白脱乙酰酶 1 (HDAC1) 可以保护基因组免受 DNA 损伤。我们发现阿霉素特异性下调 HDAC1 蛋白表达，并将 HDAC1 确定为 miR-520h 的靶标，而阿霉素上调 miR-520h。外源性 HDAC1 或 miR-520h 抑制剂会损害阿霉素诱导的细胞死亡。此外，HDAC1 通过阻止阿霉素与 DNA 的相互作用来降低 γH2AX 的水平。总之，阿霉素通过诱导 HDAC1 靶向 miR-520h 的表达来下调 HDAC1 蛋白表达，从而加剧 DNA-阿霉素相互作用。 HDAC1 蛋白的上调可能有助于人类癌细胞的耐药性，而靶向 HDAC1 是提高 DNA 损伤诱导化疗药物临床疗效的一种有前景的策略。
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.