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Blood, 1 November 2006, Vol. 108, No. 9, pp. 2887-2888.

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InsideBlood

HEMOSTASIS

Comment on Poliseno et al, page 3068

MicroRNAs control angiogenesis

Cesare Peschle

ISTITUTO SUPERIORE DI SANITÀ

The elegant report by Poliseno and colleagues indicates for the first time the functional role of microRNAs (miRNAs) in endothelial cells. Specifically, they identify miR-221 and miR-222 as key players in the control of angiogenesis, showing that they modulate the expression of kit receptor in human umbilical vein endothelial cells (HUVECs) and hence the angiogenic properties of the kit ligand, also called stem cell factor.

MicroRNAs (miRNAs) are a novel regulatory class of noncoding, single-stranded RNAs of approximately 22 nucleotides, that have been identified in plants and animals.1 miRNAs repress protein expression at posttranscriptional level, mostly through base pairing to the 3' untranslated region (UTR) of the target mRNA, thus leading to its degradation and/or reduced translation. miRNAs have been shown to control basic biologic functions, such as cell growth and differentiation. Despite these advances, few targets for the approximately 300 known mammalian miRNAs have been validated so far, hampering delineation of miRNA-based regulatory circuitries.

Little is known on the role of miRNAs in hematopoietic2 and endothelial cells. Interestingly miR-221 and miR-222 control the growth of erythropoietic and erythroleukemic cells, as well as the hematopoietic stem cell activity, through regulation of kit receptor expression at translation level.3 The report by Poliseno and colleagues identifies a similar regulatory circuitry in endothelial cells.

A growing stream of research may unveil the functional role of miRNAs in endothelial and hematopoietic cells. In this regard, Polisena et al indicate that a series of miRNAs are expressed in endothelial cells, while at least 49 miRNAs are expressed in hematopoietic cells according to lineage- and/or stage-specific patterns (N. Felli and C.P., unpublished results, 2006). Future miRNA studies may have an extraordinary impact, not only at the basic research level but also in the biotechnology/therapy area; indeed, chemically modified anti-miRNAs (antagomirs) have been shown to effectively up-modulate the expression of diverse miRNA targets for extended time periods in vivo.4

Finally, the effects of miR-221 and miR-222 on both hematopoietic and endothelial cells through regulation of kit translation once again highlights the remarkable similarity of the expression/function of diverse growth factor receptors (Flt1, KDR, Tie2, and Kit) in hematopoietic and endothelial cells, particularly at the level of primitive cells deriving from the bipotent hemangioblast.5 {blacksquare}

References

  1. Zamore PD, Haley B. Ribo-gnome: the big world of small RNAs. Science. 2005;309: 1519-1524.[Abstract/Free Full Text]

  2. Shivdasani RA. MicroRNAs: regulators of gene expression and cell differentiation. Blood. Prepublished on August 1, 2006, as DOI 10.1182/blood-2006-01-030015.[Abstract/Free Full Text]

  3. Felli N, Fontana L, Pelosi E, et al. MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. Proc Natl Acad Sci U S A. 2005;102: 18081-18086.[Abstract/Free Full Text]

  4. Krutzfeldt J, Rajewsky N, Braich R, et al. Silencing of microRNAs in vivo with `antagomirs.' Nature. 2005;438: 685-689.[CrossRef][Medline] [Order article via Infotrieve]

  5. Pelosi E, Valtieri M, Coppola S, et al. Identification of the hemangioblast in postnatal life. Blood. 2002;100: 3203-3208.[Abstract/Free Full Text]


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Related Article in Blood Online:

MicroRNAs modulate the angiogenic properties of HUVECs
Laura Poliseno, Andrea Tuccoli, Laura Mariani, Monica Evangelista, Lorenzo Citti, Keith Woods, Alberto Mercatanti, Scott Hammond, and Giuseppe Rainaldi
Blood 2006 108: 3068-3071. [Abstract] [Full Text] [PDF]




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