Kan Casina W S, Howell Viive M, Hahn Michael A, Marsh Deborah J
Hormones and Cancer Group, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, Sydney, NSW 2065, Australia.
Genes Chromosomes Cancer. 2015 Jan;54(1):1-19. doi: 10.1002/gcc.22221. Epub 2014 Oct 3.
Ovarian cancer is the fifth most common cause of cancer death in women worldwide. Serous epithelial ovarian cancer (SEOC) is the most common and aggressive histological subtype. Widespread genomic alterations go hand-in-hand with aberrant DNA damage signaling and are a hallmark of high-grade SEOC. MicroRNAs (miRNAs) are a class of small noncoding RNA molecules that are nonrandomly distributed in the genome. They are frequently located in chromosomal regions susceptible to copy number variation (CNV) associated with malignancy that can influence their expression. Widespread changes in miRNA expression have been reported in multiple cancer types including ovarian cancer. This review examines CNV and single nucleotide polymorphisms, two common types of genomic alterations that occur in ovarian cancer, in the context of their influence on the expression of miRNA and the ability of miRNA to bind to and regulate their target genes. This includes genes encoding proteins involved in DNA repair and the maintenance of genomic stability. Improved understanding of mechanisms of miRNA dysregulation and the role of miRNA in ovarian cancer will provide further insight into the pathogenesis and treatment of this disease.
卵巢癌是全球女性癌症死亡的第五大常见原因。浆液性上皮性卵巢癌（SEOC）是最常见且侵袭性最强的组织学亚型。广泛的基因组改变与异常的DNA损伤信号传导相伴，是高级别SEOC的一个标志。微小RNA（miRNA）是一类小的非编码RNA分子，它们在基因组中呈非随机分布。它们经常位于与恶性肿瘤相关的易发生拷贝数变异（CNV）的染色体区域，而这种变异会影响它们的表达。在包括卵巢癌在内的多种癌症类型中，均已报道了miRNA表达的广泛变化。本综述在基因组改变对miRNA表达的影响以及miRNA与靶基因结合并调控靶基因能力的背景下，研究了拷贝数变异（CNV）和单核苷酸多态性这两种在卵巢癌中发生的常见基因组改变类型。这包括编码参与DNA修复和维持基因组稳定性的蛋白质的基因。对miRNA失调机制以及miRNA在卵巢癌中作用的深入了解，将为该疾病的发病机制和治疗提供进一步的见解。
