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作为癌症治疗靶点的微小RNA对DNA损伤反应的调控

DNA damage response regulation by microRNAs as a therapeutic target in cancer.

作者信息

Majidinia Maryam, Yousefi Bahman

机构信息

Department of Clinical Biochemistry, Faculty of Medicine, Urmia University Medical Sciences, Urmia, Iran; Molecular Targeting Therapy Research Group, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Molecular Targeting Therapy Research Group, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

DNA Repair (Amst). 2016 Nov;47:1-11. doi: 10.1016/j.dnarep.2016.09.003. Epub 2016 Sep 27.

Abstract

The inability of cancer cells in taking care of DNA damages can lead to cancer development and/or progression. Due to the essential role of DNA repair in maintaining genomic stability, tightly controlled regulatory mechanism are required for these processes. Recent studies have shown a myriad of interactions among DNA damage response (DDR) components and miRNAs. While DDR modulates miRNA expression in transcriptional and post-transcriptional levels and affects miRNA degradation, miRNAs in turn, directly modulate the expression of multiple proteins in the DDR pathways, or indirectly fine-tune the expression of such proteins. A better understanding of DDR-miRNA interactions can facilitate the development of new anticancer agents targeting miRNAs involved in the DNA repair process. In this review, we provide a brief introduction about miRNA biogenesis and functions, DDR pathways, and recent findings about DDR-microRNA interactions. Finally, the therapeutic importance of miRNAs in modulation of DDR/DNA repair mechanisms will be discussed.

摘要

癌细胞无法处理DNA损伤会导致癌症的发生和/或进展。由于DNA修复在维持基因组稳定性中起着至关重要的作用,这些过程需要严格控制的调节机制。最近的研究表明,DNA损伤反应(DDR)成分与微小RNA(miRNA)之间存在无数相互作用。虽然DDR在转录和转录后水平上调节miRNA表达并影响miRNA降解,但miRNA反过来直接调节DDR途径中多种蛋白质的表达,或间接微调这些蛋白质的表达。更好地理解DDR与miRNA的相互作用有助于开发针对参与DNA修复过程的miRNA的新型抗癌药物。在本综述中,我们简要介绍了miRNA的生物发生和功能、DDR途径以及DDR与微小RNA相互作用的最新发现。最后,将讨论miRNA在调节DDR/DNA修复机制中的治疗重要性。

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