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Comprehensive analysis of mammalian miRNA* species and their role in myeloid cells.

Artikel i vetenskaplig tidskrift
Författare Florian Kuchenbauer
Sarah M Mah
Michael Heuser
Andrew McPherson
Jens Rüschmann
Arefeh Rouhi
Tobias Berg
Lars Bullinger
Bob Argiropoulos
Ryan D Morin
David Lai
Daniel T Starczynowski
Aly Karsan
Connie J Eaves
Akira Watahiki
Yuzhuo Wang
Samuel A Aparicio
Arnold Ganser
Jürgen Krauter
Hartmut Döhner
Konstanze Döhner
Marco A Marra
Fernando D Camargo
Lars Palmqvist
Christian Buske
R Keith Humphries
Publicerad i Blood
Volym 118
Nummer/häfte 12
Sidor 3350-8
ISSN 1528-0020
Publiceringsår 2011
Publicerad vid Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin
Sidor 3350-8
Språk en
Länkar dx.doi.org/10.1182/blood-2010-10-31...
Ämneskategorier Molekylär medicin (genetik och patologi), Medicinsk cellbiologi, Hematologi

Sammanfattning

Processing of pre-miRNA through Dicer1 generates an miRNA duplex that consists of an miRNA and miRNA* strand. Despite the general view that miRNA*s have no functional role, we further investigated miRNA* species in 10 deep-sequencing libraries from mouse and human tissue. Comparisons of miRNA/miRNA* ratios across the miRNA sequence libraries revealed that 50% of the investigated miRNA duplexes exhibited a highly dominant strand. Conversely, 10% of miRNA duplexes showed a comparable expression of both strands, whereas the remaining 40% exhibited variable ratios across the examined libraries, as exemplified by miR-223/miR-223* in murine and human cell lines. Functional analyses revealed a regulatory role for miR-223* in myeloid progenitor cells, which implies an active role for both arms of the miR-223 duplex. This was further underscored by the demonstration that miR-223 and miR-223* targeted the insulin-like growth factor 1 receptor/phosphatidylinositol 3-kinase axis and that high miR-223* levels were associated with increased overall survival in patients with acute myeloid leukemia. Thus, we found a supporting role for miR-223* in differentiating myeloid cells in normal and leukemic cell states. The fact that the miR-223 duplex acts through both arms extends the complexity of miRNA-directed gene regulation of this myeloid key miRNA.

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