title: MicroRNA-650 expression is influenced by immunoglobulin gene rearrangement and affects the biology of chronic lymphocytic leukemia.
abstract: MicroRNAs (miRNAs) play a key role in chronic lymphocytic leukemia as well as in normal B cells. Notably, miRNA gene encoding miR-650 and its homologs overlap with several variable (V) subgenes coding for lambda immunoglobulin (IgLλ). Recent studies describe the role of miR-650 in solid tumors, but its role in chronic lymphocytic leukemia (CLL) has not yet been studied. Our experiments demonstrate that miR-650 expression is regulated by coupled expression with its host gene for IgLλ. This coupling provides a unique yet unobserved mechanism for microRNA gene regulation. We determine that higher expression of miR-650 is associated with a favorable CLL prognosis and influences the proliferation capacity of B cells. We also establish that in B cells, miR-650 targets proteins important in cell proliferation and survival: cyclin dependent kinase 1 (CDK1), inhibitor of growth 4 (ING4), and early B-cell factor 3 (EBF3). This study underscores the importance of miR-650 in CLL biology and normal B-cell physiology.
authors.affiliation: Center of Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic. marek.mraz@email.cz
authors.forename: Marek
authors.initials: M
authors.lastname: Mraz
authors.forename: Dasa
authors.initials: D
authors.lastname: Dolezalova
authors.forename: Karla
authors.initials: K
authors.lastname: Plevova
authors.forename: Katerina
authors.initials: K
authors.lastname: Stano Kozubik
authors.forename: Veronika
authors.initials: V
authors.lastname: Mayerova
authors.forename: Katerina
authors.initials: K
authors.lastname: Cerna
authors.forename: Katerina
authors.initials: K
authors.lastname: Musilova
authors.forename: Boris
authors.initials: B
authors.lastname: Tichy
authors.forename: Sarka
authors.initials: S
authors.lastname: Pavlova
authors.forename: Marek
authors.initials: M
authors.lastname: Borsky
authors.forename: Jan
authors.initials: J
authors.lastname: Verner
authors.forename: Michael
authors.initials: M
authors.lastname: Doubek
authors.forename: Yvona
authors.initials: Y
authors.lastname: Brychtova
authors.forename: Martin
authors.initials: M
authors.lastname: Trbusek
authors.forename: Ales
authors.initials: A
authors.lastname: Hampl
authors.forename: Jiri
authors.initials: J
authors.lastname: Mayer
authors.forename: Sarka
authors.initials: S
authors.lastname: Pospisilova
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D005786:Gene Expression Regulation; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D050439:Genes, Immunoglobulin Light Chain; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis
chemical_list: C550124:MIRN650 microRNA, human; D035683:MicroRNAs