• Medientyp: E-Artikel
  • Titel: Comprehensive analysis of mammalian miRNA* species and their role in myeloid cells
  • Beteiligte: Kuchenbauer, Florian; Mah, Sarah M.; Heuser, Michael; McPherson, Andrew; Rüschmann, Jens; Rouhi, Arefeh; Berg, Tobias; Bullinger, Lars; Argiropoulos, Bob; Morin, Ryan D.; Lai, David; Starczynowski, Daniel T.; Karsan, Aly; Eaves, Connie J.; Watahiki, Akira; Wang, Yuzhuo; Aparicio, Samuel A.; Ganser, Arnold; Krauter, Jürgen; Döhner, Hartmut; Döhner, Konstanze; Marra, Marco A.; Camargo, Fernando D.; Palmqvist, Lars; [...]
  • Erschienen: American Society of Hematology, 2011
  • Erschienen in: Blood
  • Sprache: Englisch
  • DOI: 10.1182/blood-2010-10-312454
  • ISSN: 0006-4971; 1528-0020
  • Schlagwörter: Cell Biology ; Hematology ; Immunology ; Biochemistry
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title> <jats:p>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.</jats:p>
  • Zugangsstatus: Freier Zugang