title: Comprehensive analysis of mammalian miRNA* species and their role in myeloid cells.
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.
authors.affiliation: Department of Internal Medicine III, Comprehensive Cancer Centre, University Hospital of Ulm, Ulm, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Kuchenbauer
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Mah
authors.forename: Michael
authors.initials: M
authors.lastname: Heuser
authors.forename: Andrew
authors.initials: A
authors.lastname: McPherson
authors.forename: Jens
authors.initials: J
authors.lastname: Rüschmann
authors.forename: Arefeh
authors.initials: A
authors.lastname: Rouhi
authors.forename: Tobias
authors.initials: T
authors.lastname: Berg
authors.forename: Lars
authors.initials: L
authors.lastname: Bullinger
authors.forename: Bob
authors.initials: B
authors.lastname: Argiropoulos
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Morin
authors.forename: David
authors.initials: D
authors.lastname: Lai
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Starczynowski
authors.forename: Aly
authors.initials: A
authors.lastname: Karsan
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Eaves
authors.forename: Akira
authors.initials: A
authors.lastname: Watahiki
authors.forename: Yuzhuo
authors.initials: Y
authors.lastname: Wang
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Aparicio
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Jürgen
authors.initials: J
authors.lastname: Krauter
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.forename: Konstanze
authors.initials: K
authors.lastname: Döhner
authors.forename: Marco A
authors.initials: MA
authors.lastname: Marra
authors.forename: Fernando D
authors.initials: FD
authors.lastname: Camargo
authors.forename: Lars
authors.initials: L
authors.lastname: Palmqvist
authors.forename: Christian
authors.initials: C
authors.lastname: Buske
authors.forename: R Keith
authors.initials: RK
authors.lastname: Humphries
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000032:analysis / Q000096:biosynthesis; D017930:Genes, Reporter; D005822:Genetic Vectors; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008156:Luciferases / Q000032:analysis; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D023461:Myeloid Progenitor Cells / Q000378:metabolism* / Q000473:pathology; D009693:Nucleic Acid Hybridization / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012190:Retroviridae; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D054852:Small Molecule Libraries / Q000032:analysis; D015996:Survival Rate; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D035683:MicroRNAs; D011956:Receptors, Cell Surface; D054852:Small Molecule Libraries; D007334:Insulin-Like Growth Factor I; D008156:Luciferases; D019869:Phosphatidylinositol 3-Kinases; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases