title: The miR-223 host non-coding transcript linc-223 induces IRF4 expression in acute myeloid leukemia by acting as a competing endogenous RNA.
abstract: Alterations in genetic programs required for terminal myeloid differentiation and aberrant proliferation characterize acute myeloid leukemia (AML) cells. Here, we identify the host transcript of miR-223, linc-223, as a novel functional long non-coding RNA (lncRNA) in AML. We show that from the primary nuclear transcript, the alternative production of miR-223 and linc-223 is finely regulated during monocytic differentiation. Moreover, linc-223 expression inhibits cell cycle progression and promotes monocytic differentiation of AML cells. We also demonstrate that endogenous linc-223 localizes in the cytoplasm and acts as a competing endogenous RNA for miR-125-5p, an oncogenic microRNA in leukemia. In particular, we show that linc-223 directly binds to miR-125-5p and that its knockdown increases the repressing activity of miR-125-5p resulting in the downregulation of its target interferon regulatory factor 4 (IRF4), which it was previously shown to inhibit the oncogenic activity of miR-125-5p in vivo. Furthermore, data from primary AML samples show significant downregulation of linc-223 in different AML subtypes. Therein, these findings indicate that the newly identified lncRNA linc-223 may have an important role in myeloid differentiation and leukemogenesis, at least in part, by cross-talking with IRF4 mRNA.
authors: Department of Biology and Biotechnology "C. Darwiny", Sapienza University of Rome, Rome, 00185, Italy.|Present address: KAUST Environmental Epigenetics Research Program, Biological Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia.
authors: Arianna
authors: A
authors: Mangiavacchi
authors: Department of Biology and Biotechnology "C. Darwiny", Sapienza University of Rome, Rome, 00185, Italy.
authors: Melissa
authors: M
authors: Sorci
authors: Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome, 00185, Italy.
authors: Silvia
authors: S
authors: Masciarelli
authors: Department of Biology and Biotechnology "C. Darwiny", Sapienza University of Rome, Rome, 00185, Italy.
authors: Simone
authors: S
authors: Larivera
authors: Department of Biology and Biotechnology "C. Darwiny", Sapienza University of Rome, Rome, 00185, Italy.
authors: Ivano
authors: I
authors: Legnini
authors: Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome, 00185, Italy.
authors: Ilaria
authors: I
authors: Iosue
authors: Department of Biology and Biotechnology "C. Darwiny", Sapienza University of Rome, Rome, 00185, Italy.|Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Rome, 00161, Italy.|Institute Pasteur Fondazione Cenci-Bolognetti, Sapienza University of Rome, Rome, 00185, Italy.
authors: Irene
authors: I
authors: Bozzoni
authors: Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome, 00185, Italy.
authors: Francesco
authors: F
authors: Fazi
authors: Department of Biology and Biotechnology "C. Darwiny", Sapienza University of Rome, Rome, 00185, Italy.
authors: Alessandro
authors: A
authors: Fatica
mesh_terms: D000328:Adult; D000368:Aged; D002454:Cell Differentiation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015973:Gene Expression Regulation, Leukemic; D018922:HL-60 Cells; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics* / Q000378:metabolism; D020014:K562 Cells; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D062085:RNA, Long Noncoding / Q000235:genetics*; D055815:Young Adult; D000099218:Interferon Regulatory Factor-4
chemical_list: D050835:Interferon Regulatory Factors; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D000099218:Interferon Regulatory Factor-4; C531888:MIRN125 microRNA, human; C525067:MIR223, human
keywords: IRF4; acute myeloid leukemia; long non-coding RNA; miR-125