Second Department of Internal Medicine, University of Athens, University General Hospital "Attikon", Haidari, Greece.
Eur J Haematol. 2010 Jan 1;84(1):1-16. doi: 10.1111/j.1600-0609.2009.01348.x. Epub 2009 Sep 10.
MicroRNAs are small non-coding RNAs that act at the post-transcriptional level, regulating protein expression by repressing translation or destabilizing mRNA target. Because of their discovery, microRNAs have been associated with almost every normal cell function, including proliferation, differentiation and apoptosis. Several lines of evidence suggest that they have an important role in normal hematopoiesis as exemplified by the role of mir-155 and mir-150 in the differentiation of B and T lymphocytes, the suppressive role of mir-221 and mir-222 in erythroid differentiation, the inhibitory effect of mir-181 on hematopoietic differentiation and the induction of myeloid differentiation by mir-223. Moreover, they play a role both as oncogenes, probably by a variety of mechanisms, namely through elimination of tumor suppressor proteins, or as tumor suppressor genes by targeting oncogenic mRNAs. Their aberrant expression has been associated with solid tumors and hematopoietic malignancies as suggested by the frequent deletion of mir-15a and mir-16-1 in chronic lymphocytic leukemia, the increased levels of mir-155 in diffuse large B-cell lymphomas and the increased levels of mir-181 in acute myeloid leukemia M1 and M2. The purpose of this review is to summarize current knowledge on the role of microRNAs in normal hematopoiesis and hematopoietic malignancies and, moreover, to highlight their role as potential therapeutic tools.
微小 RNA 是一种小的非编码 RNA,在转录后水平发挥作用,通过抑制翻译或使 mRNA 靶标不稳定来调节蛋白质表达。由于它们的发现,微小 RNA 与几乎所有正常的细胞功能都有关联,包括增殖、分化和凋亡。有几条证据表明它们在正常造血中起着重要作用,例如 mir-155 和 mir-150 在 B 和 T 淋巴细胞分化中的作用,mir-221 和 mir-222 在红细胞分化中的抑制作用,mir-181 对造血分化的抑制作用以及 mir-223 诱导髓系分化。此外,它们既可以作为癌基因发挥作用,可能通过多种机制,即通过消除肿瘤抑制蛋白,也可以作为肿瘤抑制基因,通过靶向致癌 mRNA。它们的异常表达与实体瘤和造血恶性肿瘤有关,如慢性淋巴细胞白血病中 mir-15a 和 mir-16-1 的频繁缺失,弥漫性大 B 细胞淋巴瘤中 mir-155 的水平升高,以及急性髓系白血病 M1 和 M2 中 mir-181 的水平升高。本综述的目的是总结微小 RNA 在正常造血和造血恶性肿瘤中的作用的现有知识,并且强调它们作为潜在治疗工具的作用。