Barbarotto Elisa, Calin George A
Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Curr Pharm Des. 2008;14(21):2040-50. doi: 10.2174/138161208785294627.
MicroRNAs (miRNAs) are an abundant class of approximately 22-nucleotide-noncoding RNAs, which play important regulatory roles in animal and plant development: they are involved in gene expression at the posttranscriptional level by degrading or blocking translation of messenger RNA (mRNA) targets. miRNAs can induce RNA cleavage and chromatin modifications, and are implicated in apoptotic pathways and regulation of cell growth and proliferation. It is becoming clear that miRNAs play important roles in the regulation of gene expression during development, and our knowledge of the expression levels or function of miRNAs in normal and neoplastic cells is increasing. Accumulating experimental evidence suggests that different miRNAs are deregulated in primary human tumors and that many human miRNAs are located at genomic regions linked to cancer. miRNAs may be important regulators of mammalian hematopoiesis. They are involved in a variety of hematological malignancies, including acute lymphoblastic leukemia, acute myeloid leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, diffuse large B-cell lymphoma, and primary effusion lymphoma. Here, we provide background on the biogenesis and function of miRNAs and discuss potential therapeutic applications of miRNA-based technology in hematological malignancies.
微小RNA(miRNA)是一类丰富的约22个核苷酸的非编码RNA,在动植物发育中发挥重要的调控作用:它们通过降解或阻断信使RNA(mRNA)靶标的翻译在转录后水平参与基因表达。miRNA可诱导RNA切割和染色质修饰,并与凋亡途径以及细胞生长和增殖的调控有关。越来越清楚的是,miRNA在发育过程中的基因表达调控中发挥重要作用,并且我们对正常细胞和肿瘤细胞中miRNA的表达水平或功能的了解也在增加。越来越多的实验证据表明,不同的miRNA在原发性人类肿瘤中失调,并且许多人类miRNA位于与癌症相关的基因组区域。miRNA可能是哺乳动物造血的重要调节因子。它们参与多种血液系统恶性肿瘤,包括急性淋巴细胞白血病、急性髓细胞白血病、慢性粒细胞白血病、慢性淋巴细胞白血病、弥漫性大B细胞淋巴瘤和原发性渗出性淋巴瘤。在此,我们提供miRNA生物发生和功能的背景知识,并讨论基于miRNA的技术在血液系统恶性肿瘤中的潜在治疗应用。