Dept. of Veterinary Morphophysiology, Grugliasco (TO), University of Turin, Italy.
Mini Rev Med Chem. 2011 Nov;11(13):1165-82. doi: 10.2174/138955711797655371.
MicroRNAs (miRNAs) are approximately 22 nucleotide endogenous RNA molecules which exert their functions by base pairing with messenger RNAs (mRNAs), thereby regulating protein-coding gene expression. In eukaryotic cells, miRNAs play important roles in regulating biological processes such as proliferation, differentiation, apoptosis, and stem cell self-renewal. miRNAs are encoded by the genome, and more than 1,000 human miRNAs have been identified so far. miRNAs are predicted to target -60% of human mRNAs and are expressed in all animal cells. Unique expression domains, targets, and gain- and loss-of-function phenotypes of particular miRNAs have important implications for directed to control differentiation of stem cell populations. Many cancers show variations in miRNA levels, and more specifically an overall downregulation, when compared to their normal counterparts. Therefore, miRNAs may be used as potential therapeutic agents to correct aberrant transcript levels found in the signaling pathways of cancer. This review examines the most recent acquisition on the role of miRNAs in regulating the cell cycle, with particular emphasis on their effects on cell proliferation and differentiation. The second part explores specifically the role of these factors in the physiological regulation of embryonic stem cells, of cellular reprogramming and their involvement in the activation of stem cells in adult tissues. In the third part, the article discusses some issues that relate to the role of miRNAs in the development of neoplastic diseases, focusing on aspects of the genetic and transcriptional alterations that determine the beginning and the development of tumor process, with emphasis on, looking to emphasize their involvement in the activation of adult cancer stem cells.
微小 RNA(miRNA)是大约 22 个核苷酸的内源性 RNA 分子,通过与信使 RNA(mRNA)碱基配对发挥作用,从而调节蛋白质编码基因的表达。在真核细胞中,miRNA 在调节增殖、分化、凋亡和干细胞自我更新等生物过程中发挥着重要作用。miRNA 由基因组编码,目前已经鉴定出超过 1000 个人类 miRNA。miRNA 被预测靶向 -60%的人类 mRNAs,并在所有动物细胞中表达。特定 miRNA 的独特表达域、靶标和功能获得和缺失表型对指导干细胞群体的分化具有重要意义。许多癌症的 miRNA 水平发生变化,与正常对照相比,总体下调。因此,miRNA 可能被用作潜在的治疗剂来纠正癌症信号通路中异常的转录水平。本综述检查了 miRNA 在调节细胞周期中的最新作用,特别强调了它们对细胞增殖和分化的影响。第二部分专门探讨了这些因素在胚胎干细胞的生理调节、细胞重编程及其在成年组织中干细胞激活中的作用。在第三部分,文章讨论了 miRNA 在肿瘤疾病发展中的作用的一些问题,重点关注决定肿瘤过程开始和发展的遗传和转录改变的方面,强调它们在激活成年癌症干细胞中的作用。