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Targeting the microRNA-regulating DNA damage/repair pathways in cancer

机译：针对癌症中调控microRNA的DNA损伤/修复途径

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Introduction: Maintenance of genome stability requires the integrity of the DNA repair machinery. DNA damage response (DDR) determines cell fate and regulates the expression of microRNAs (miRNAs), which in turn may also regulate important components of the DNA repair machinery. Areas covered: In this review, we describe the bidirectional connection between miRNAs and DDR and their link with important biological functions such as, DNA repair, cell cycle and apoptosis in cancer. Furthermore, we highlight the potential implications of recent findings on miRNA/DDR in determining chemotherapy response in cancer patients, and the use of these biomarkers for novel potential therapeutic approaches. Expert opinion: Defects in the DDR and deregulation of miRNAs are important hallmarks of human cancer. A full understanding of the mechanisms underlying the connection between miRNAs and DDR/DNA repair pathways will positively impact our knowledge on human tumor biology and on different responses to distinct drugs. Specific miRNAs interact with distinct DDR components and are promising targets for enhancing the effects of, and/or to overcome the resistance to, conventional chemotherapeutic agents. Finally, the development of innovative tools to deliver miRNA-targeting oligonucleotides may represents novel types of cancer interventions in clinic.
机译：简介：维持基因组稳定性需要DNA修复机制的完整性。 DNA损伤反应（DDR）决定细胞命运并调节microRNA（miRNA）的表达，而microRNA的表达又可以调节DNA修复机制的重要组成部分。涵盖的领域：在这篇综述中，我们描述了miRNA与DDR之间的双向连接以及它们与重要的生物学功能（如DNA修复，细胞周期和癌症中的凋亡）的联系。此外，我们强调了miRNA / DDR最新发现对确定癌症患者化疗反应的潜在影响，以及将这些生物标记物用于新的潜在治疗方法。专家意见：DDR缺陷和miRNA失控是人类癌症的重要标志。对miRNA与DDR / DNA修复途径之间联系的潜在机制的充分理解将对我们对人类肿瘤生物学以及对不同药物的不同反应的认识产生积极影响。特定的miRNA与独特的DDR成分相互作用，是增强常规化学治疗剂作用和/或克服常规化学治疗剂耐药性的有希望的靶标。最后，开发用于靶向miRNA的寡核苷酸的创新工具可能代表了临床上新型的癌症干预措施。

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