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微小RNA在卵巢癌基因组稳定性和应激反应中的当前意义

Current Implications of microRNAs in Genome Stability and Stress Responses of Ovarian Cancer.

作者信息

Gajek Arkadiusz, Gralewska Patrycja, Marczak Agnieszka, Rogalska Aneta

机构信息

Department of Medical Biophysics, Faculty of Biology and Environmental Protection, Institute of Biophysics, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.

出版信息

Cancers (Basel). 2021 May 29;13(11):2690. doi: 10.3390/cancers13112690.

Abstract

Genomic alterations and aberrant DNA damage signaling are hallmarks of ovarian cancer (OC), the leading cause of mortality among gynecological cancers worldwide. Owing to the lack of specific symptoms and late-stage diagnosis, survival chances of patients are significantly reduced. Poly (ADP-ribose) polymerase (PARP) inhibitors and replication stress response inhibitors present attractive therapeutic strategies for OC. Recent research has focused on ovarian cancer-associated microRNAs (miRNAs) that play significant regulatory roles in various cellular processes. While miRNAs have been shown to participate in regulation of tumorigenesis and drug responses through modulating the DNA damage response (DDR), little is known about their potential influence on sensitivity to chemotherapy. The main objective of this review is to summarize recent findings on the utility of miRNAs as cancer biomarkers, in particular, ovarian cancer, and their regulation of DDR or modified replication stress response proteins. We further discuss the suppressive and promotional effects of various miRNAs on ovarian cancer and their participation in cell cycle disturbance, response to DNA damage, and therapeutic functions in multiple cancer types, with particular focus on ovarian cancer. Improved understanding of the mechanisms by which miRNAs regulate drug resistance should facilitate the development of effective combination therapies for ovarian cancer.

摘要

基因组改变和异常的DNA损伤信号传导是卵巢癌(OC)的标志,卵巢癌是全球妇科癌症中导致死亡的主要原因。由于缺乏特异性症状和晚期诊断,患者的生存机会显著降低。聚(ADP-核糖)聚合酶(PARP)抑制剂和复制应激反应抑制剂为卵巢癌提供了有吸引力的治疗策略。最近的研究集中在与卵巢癌相关的微小RNA(miRNA)上,它们在各种细胞过程中发挥着重要的调节作用。虽然已表明miRNA通过调节DNA损伤反应(DDR)参与肿瘤发生和药物反应的调控,但对其对化疗敏感性的潜在影响知之甚少。本综述的主要目的是总结关于miRNA作为癌症生物标志物,特别是卵巢癌生物标志物的效用及其对DDR或修饰的复制应激反应蛋白的调控的最新发现。我们进一步讨论了各种miRNA对卵巢癌的抑制和促进作用,以及它们在细胞周期紊乱、对DNA损伤的反应和多种癌症类型(特别是卵巢癌)的治疗功能中的参与情况。对miRNA调节耐药性机制的更好理解应有助于开发有效的卵巢癌联合治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0e4/8199164/7ed0a4793638/cancers-13-02690-g001.jpg

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