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首页> 外文期刊>Cancer Cell >Delta Np63/DGCR8-Dependent MicroRNAs Mediate Therapeutic Efficacy of HDAC Inhibitors in Cancer
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Delta Np63/DGCR8-Dependent MicroRNAs Mediate Therapeutic Efficacy of HDAC Inhibitors in Cancer

机译:Delta Np63 / DGCR8依赖性MicroRNA介导HDAC抑制剂在癌症中的治疗功效。

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摘要

Delta Np63 is an oncogenic member of the p53 family and acts to inhibit the tumor-suppressive activities of the p53 family. By performing a chemical library screen, we identified histone deacetylase inhibitors (HDACi) as agents reducing Delta Np63 protein stability through the E3 ubiquitin ligase, Fbw7. Delta Np63 inhibition decreases the levels of its transcriptional target, DGCR8, and the maturation of let-7d and miR-128, which we found to be critical for HDACi function in vitro and in vivo. Our work identified Fbw7 as a predictive marker for HDACi response in squamous cell carcinomas and lymphomas, and unveiled let-7d and miR-128 as specific targets to bypass tumor resistance to HDACi treatment.
机译:Delta Np63是p53家族的致癌成员,可抑制p53家族的肿瘤抑制活性。通过执行化学文库筛选,我们确定了组蛋白脱乙酰基酶抑制剂(HDACi)是通过E3泛素连接酶Fbw7降低Delta Np63蛋白稳定性的试剂。 Delta Np63抑制作用会降低其转录靶标DGCR8的水平,以及let-7d和miR-128的成熟,这对于体外和体内HDACi功能至关重要。我们的工作确定了Fbw7是鳞状细胞癌和淋巴瘤中HDACi反应的预测标记,并揭示了let-7d和miR-128作为绕过HDACi治疗的肿瘤耐药性的特异性靶标。

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