Giannakakis Antonis, Coukos George, Hatzigeorgiou Artemis, Sandaltzopoulos Raphael, Zhang Lin
University of Pennsylvania School of Medicine, Center for Research on Early Detection and Cure of Ovarian Cancer, Rm1209 BRB II/III, 421 Curie Blvd., Philadelphia, PA 19104, USA.
Expert Opin Biol Ther. 2007 Sep;7(9):1375-86. doi: 10.1517/14712598.7.9.1375.
MicroRNAs (miRNAs) are endogenous, non-coding, small RNAs, which negatively regulate gene expression in a sequence-specific manner via translational repression and/or mRNA degradation. Their discovery revealed a new and exciting aspect of post-transcriptional gene regulation that is universally involved in cellular homeostasis. Importantly, the advent of miRNAs added another level of complication in the already complex regulatory networks of the cell, undermining that RNA molecules in general, should be considered gene regulators of equal importance with proteins. Recently, the scientific community drew attention to the miRNA field for an additional reason: an increasing line of evidence indicated that miRNA genes are tightly connected with the process of tumorigenesis. Indeed, several miRNAs have already been demonstrated to behave as oncogenes or tumor suppressor genes in many types of cancer. Even though the underlying mechanisms by which miRNAs can destabilize the normal cellular processes, promoting cell transformation and tumor progression, are not well understood, genetic and epigenetic alterations most probably play a critical role. Significant technologic advances facilitated the profiling of the miRNA expression patterns in normal and cancer tissues and discovered an unexpected greater reliability of miRNA expression signatures in classifying cancer types than the respective signatures of protein-coding genes. Along with this extraordinary diagnostic potential, miRNAs have also proved their prognostic value in predicting clinical behaviors of cancer patients. The aim of this review is to describe miRNA expression and how its deregulation is involved in the pathophysiology of human cancers.
微小RNA(miRNA)是内源性非编码小RNA,通过翻译抑制和/或mRNA降解以序列特异性方式负调控基因表达。它们的发现揭示了转录后基因调控的一个新的、令人兴奋的方面,这一过程普遍参与细胞稳态。重要的是,miRNA的出现给细胞中本已复杂的调控网络增加了另一层复杂性,这表明一般而言,RNA分子应被视为与蛋白质同等重要的基因调控因子。最近,科学界关注miRNA领域还有另一个原因:越来越多的证据表明miRNA基因与肿瘤发生过程紧密相关。事实上,在许多类型的癌症中,已有几种miRNA被证明具有癌基因或肿瘤抑制基因的作用。尽管miRNA破坏正常细胞过程、促进细胞转化和肿瘤进展的潜在机制尚未完全明确,但遗传和表观遗传改变很可能起着关键作用。重大的技术进步促进了对正常组织和癌组织中miRNA表达模式的分析,并发现与蛋白质编码基因各自的特征相比,miRNA表达特征在癌症类型分类中具有更高的可靠性。除了这种非凡的诊断潜力外,miRNA在预测癌症患者临床行为方面也已证明了其预后价值。本综述的目的是描述miRNA的表达及其失调如何参与人类癌症的病理生理学过程。