microrna在正常造血和人类白血病中的意义

Muller Fabbri , Ramiro Garzon
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摘要

MicroRNAs (miRNAs)是一种小的非编码rna,具有重要的调节功能,包括造血分化。高通量检测miRNA表达方法的出现,使得研究正常造血过程中的miRNA水平成为可能,并揭示了白血病细胞中相对于正常造血细胞广泛存在的miRNA异常表达,提示miRNA在人类白血病发生中的作用。研究表明,mirna确实参与了人类白血病的发生和发展。miRNA基因及其靶位点的突变可通过改变miRNA表达或影响其对靶信使RNA的调节功能而诱发癌症。此外,miRNA表达谱还可以独立于其他生物标志物区分预后不良的白血病患者。在此,我们回顾了研究mirna在正常人类造血以及急性和慢性白血病中的作用的主要研究。此外,我们将讨论其他非编码rna(即超保守区域)在白血病中的新作用。
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Implications of MicroRNAs in Normal Hematopoiesis and Human Leukemia

MicroRNAs (miRNAs) are small noncoding RNAs with important regulatory functions, including hematopoietic differentiation. The advent of high-throughput methods to detect miRNA expression has allowed the study of miRNA levels during normal hematopoiesis and have revealed a widespread aberrant miRNA expression in leukemic cells with respect to the normal hematopoietic cells, suggesting a role for miRNAs in human leukemogenesis. Studies have demonstrated that miRNAs are indeed involved in the initiation and progression of human leukemias. Mutations in miRNA genes and in their target sites could predispose to cancer by altering miRNA expression or by affecting its regulatory function on the target messenger RNA. Furthermore, miRNA expression profiling could also distinguish patients with leukemia with poor outcome independent from other biomarkers. Herein, we review the main studies investigating the role of miRNAs in normal human hematopoiesis as well as in acute and chronic leukemias. In addition, we will discuss the emerging role of other noncoding RNAs (namely the ultraconserved regions) in leukemia.

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