The miR-223 host non-coding transcript linc-223 induces IRF4 expression in acute myeloid leukemia by acting as a competing endogenous RNA

Silvia Masciarelli, Arianna Mangiavacchi, Melissa Sorci, Simone Larivera, Ivano Legnini, Ilaria Iosue, Irene Bozzoni, Francesco Fazi, Alessandro Fatica

Risultato della ricerca: Contributo in rivistaArticolo in rivista

25 Citazioni (Scopus)

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 noncoding 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.
Lingua originaleEnglish
pagine (da-a)60155-60168
Numero di pagine14
RivistaOncotarget
Volume7
DOI
Stato di pubblicazionePubblicato - 2016

Keywords

  • Acute myeloid leukemia
  • Adult
  • Aged
  • Cell Differentiation
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Leukemic
  • HL-60 Cells
  • Humans
  • IRF4
  • Interferon Regulatory Factors
  • K562 Cells
  • Leukemia, Myeloid, Acute
  • Long non-coding RNA
  • Male
  • MiR-125
  • MicroRNAs
  • Middle Aged
  • RNA, Long Noncoding
  • Young Adult

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