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.

The miR-223 host non-coding transcript linc-223 induces IRF4 expression in acute myeloid leukemia by acting as a competing endogenous RNA / Mangiavacchi, Arianna; Sorci, Melissa; Masciarelli, Silvia; Larivera, Simone; Legnini, Ivano; Iosue', Ilaria; Bozzoni, Irene; Fazi, Francesco; Fatica, Alessandro. - In: ONCOTARGET. - ISSN 1949-2553. - STAMPA. - 7:37(2016), pp. 60155-60168. [10.18632/oncotarget.11165]

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

MANGIAVACCHI, ARIANNA;SORCI, MELISSA;MASCIARELLI, SILVIA;LEGNINI, IVANO;IOSUE', ILARIA;BOZZONI, Irene;FAZI, Francesco;FATICA, Alessandro
2016

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.
2016
acute myeloid leukemia; IRF4; long non-coding RNA; miR-125; oncology
01 Pubblicazione su rivista::01a Articolo in rivista
The miR-223 host non-coding transcript linc-223 induces IRF4 expression in acute myeloid leukemia by acting as a competing endogenous RNA / Mangiavacchi, Arianna; Sorci, Melissa; Masciarelli, Silvia; Larivera, Simone; Legnini, Ivano; Iosue', Ilaria; Bozzoni, Irene; Fazi, Francesco; Fatica, Alessandro. - In: ONCOTARGET. - ISSN 1949-2553. - STAMPA. - 7:37(2016), pp. 60155-60168. [10.18632/oncotarget.11165]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/900283
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