Unit of Molecular Therapies, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Int J Biochem Cell Biol. 2010 Aug;42(8):1262-72. doi: 10.1016/j.biocel.2009.12.017. Epub 2009 Dec 24.
Despite important improvements over the past two decades, the overall cure rate of epithelial ovarian cancer (EOC) remains only approximately 30%. Although much has been learned about the proteins and pathways involved in early events of malignant transformation and drug resistance, a major challenge still remaining is the identification of markers for early diagnosis and prediction of response to chemotherapy. Recently, it has become clear that alterations in the expression of microRNAs (miRNAs) contribute to the pathogenesis and progression of several human malignancies. In this review we discuss current data concerning the accumulating evidence of the role of miRNAs in EOC pathogenesis and tumor characterization; their dysregulated expression in EOC; and their still undefined role in diagnosis, prognosis and prediction of response to therapy. The most frequently deregulated miRNAs are members of the let-7 and miR-200 families, the latter involved in epithelial-to-mesenchymal transition (EMT). EMT is part of normal ovarian surface epithelium physiology, being the key regulator of the post-ovulatory repair process, and failure to undergo EMT may be one of the events leading to transformation. A general down-modulation of miRNA expression is observed in EOC compared to normal tissue. However, a clear consensus on the miRNA signatures associated with prognosis or prediction of response to therapy has not yet been reached.
尽管在过去的二十年中取得了重要进展，但上皮性卵巢癌 (EOC) 的总体治愈率仍仅约为 30%。尽管已经了解了许多涉及恶性转化和耐药性早期事件的蛋白质和途径，但仍然存在一个主要挑战，即确定用于早期诊断和预测化疗反应的标志物。最近，已经清楚的是，miRNAs（miRNA）表达的改变有助于几种人类恶性肿瘤的发病机制和进展。在这篇综述中，我们讨论了 miRNA 在 EOC 发病机制和肿瘤特征中的作用的累积证据；它们在 EOC 中的失调表达；以及它们在诊断、预后和预测治疗反应中的作用仍未定义。最常失调的 miRNA 是 let-7 和 miR-200 家族的成员，后者参与上皮间质转化 (EMT)。EMT 是正常卵巢表面上皮生理学的一部分，是排卵后修复过程的关键调节剂，而不能进行 EMT 可能是导致转化的事件之一。与正常组织相比，EOC 中 miRNA 表达普遍下调。然而，尚未就与预后或预测治疗反应相关的 miRNA 特征达成明确共识。
