Ovarian cancer (OvCa) is one of the most life-threatening female malignancies that affects 300,000 women annually worldwide. Impaired mechanisms of DNA repair are the leading cause of mutations underlying the OvCa development. microRNAs are short non-coding RNAs that regulate the expression of genes by binding to their transcripts and inducing mRNA degradation or inhibition of translation. Here, we review the miRNA-mediated dysregulation of genes involved in DNA damage response (DDR) and DNA repair pathways in OvCa. Apparently, miRNAs are capable of targeting the crucial mediators of DDR (e.g., miR-203a-3p targeting ATM (Ataxia Telangiectasia Mutated)), homologous repair (such as BRCA1 targeted by miR-9, miR-1255b, miR-193b, and miR-148b), non-homologous end joining (with RNF8 being regulated by miR-214), nucleotide excision repair (involving DDB2 targeted by miR-328-3p), or translesion DNA synthesis (involving RAD18, participating also in homologous repair and targeted by miR-379-5p). We also discuss miRNAs (such as miR-519a-3p, let-7e, miR-216b), which affect responses to OvCa therapy by targeting PARP1 (Poly(ADP-Ribose) Polymerase-1). Finally, we also discuss why, despite the identification of multiple miRNAs capable of regulating DNA repair genes, as well as those involved in the response to therapy, no miRNA-based drugs have been approved for OvCa treatment in clinics.
卵巢癌是全球范围内每年影响30万女性的最具致命性的妇科恶性肿瘤之一。DNA修复机制受损是导致卵巢癌发生突变的主要原因。microRNA是一类短链非编码RNA，通过结合靶基因转录本并诱导mRNA降解或翻译抑制来调控基因表达。本文综述了卵巢癌中miRNA介导的DNA损伤应答及DNA修复通路相关基因的调控异常。研究表明，miRNA能够靶向调控DNA损伤应答关键介质（如miR-203a-3p靶向ATM基因）、同源重组修复（如BRCA1受miR-9、miR-1255b、miR-193b和miR-148b调控）、非同源末端连接（如RNF8受miR-214调控）、核苷酸切除修复（如DDB2受miR-328-3p靶向）或跨损伤DNA合成（如同时参与同源重组修复的RAD18受miR-379-5p调控）。我们还探讨了通过靶向PARP1影响卵巢癌治疗反应的miRNA（如miR-519a-3p、let-7e、miR-216b）。最后，本文分析了为何尽管已发现多种能够调控DNA修复基因及治疗反应相关基因的miRNA，但目前尚无基于miRNA的药物获批用于临床卵巢癌治疗。
肿瘤(癌症)患者之家