Year: 2011
Type: article
Abstract: 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.
Source: Blood
Authors: 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
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2096513091