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

Handle URI:
http://hdl.handle.net/10754/621271
Title:
The miR-223 host non-coding transcript linc-223 induces IRF4 expression in acute myeloid leukemia by acting as a competing endogenous RNA
Authors:
Mangiavacchi, Arianna; Sorci, Melissa; Masciarelli, Silvia; Larivera, Simone; Legnini, Ivano; Iosue, Ilaria; Bozzoni, Irene; Fazi, Francesco; Fatica, Alessandro
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.
KAUST Department:
KAUST Environmental Epigenetics Research Program (KEEP)
Citation:
Mangiavacchi A, Sorci M, Masciarelli S, Larivera S, Legnini I, et al. (2016) The miR-223 host non-coding transcript linc-223 induces IRF4 expression in acute myeloid leukemia by acting as a competing endogenous RNA. Oncotarget. Available: http://dx.doi.org/10.18632/oncotarget.11165.
Publisher:
Impact Journals, LLC
Journal:
Oncotarget
Issue Date:
10-Aug-2016
DOI:
10.18632/oncotarget.11165
Type:
Article
ISSN:
1949-2553
Sponsors:
The authors would like to thank Dr A. Rosa and Dr A. Brivanlou for the ePiggyBac inducible transposon system, A Sorrentino for the RNA from the human CD34+ progenitor cells, and M. Marchioni and M. Arceci for technical assistance. This work was supported by A.I.R.C. (IG 17352) and “Progetti Ateneo” Sapienza University of Rome to A.F.; and ERC-2013 (AdG 340172–MUNCODD), Epigen-Epigenomics Flagship Project, AFM-Telethon (17835), PRIN 2013, AriSLA full grant 2014 “ARCI” and HFSP (RGP0009/2014) to I.B. Contribution of AIRC (StG 4841) and FILAS-RU-2014-1020 to FF was greatly appreciated.
Additional Links:
http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=11165
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Articles

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DC FieldValue Language
dc.contributor.authorMangiavacchi, Ariannaen
dc.contributor.authorSorci, Melissaen
dc.contributor.authorMasciarelli, Silviaen
dc.contributor.authorLarivera, Simoneen
dc.contributor.authorLegnini, Ivanoen
dc.contributor.authorIosue, Ilariaen
dc.contributor.authorBozzoni, Ireneen
dc.contributor.authorFazi, Francescoen
dc.contributor.authorFatica, Alessandroen
dc.date.accessioned2016-11-03T07:43:57Z-
dc.date.available2016-11-03T07:43:57Z-
dc.date.issued2016-08-10en
dc.identifier.citationMangiavacchi A, Sorci M, Masciarelli S, Larivera S, Legnini I, et al. (2016) The miR-223 host non-coding transcript linc-223 induces IRF4 expression in acute myeloid leukemia by acting as a competing endogenous RNA. Oncotarget. Available: http://dx.doi.org/10.18632/oncotarget.11165.en
dc.identifier.issn1949-2553en
dc.identifier.doi10.18632/oncotarget.11165en
dc.identifier.urihttp://hdl.handle.net/10754/621271-
dc.description.abstractAlterations 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.en
dc.description.sponsorshipThe authors would like to thank Dr A. Rosa and Dr A. Brivanlou for the ePiggyBac inducible transposon system, A Sorrentino for the RNA from the human CD34+ progenitor cells, and M. Marchioni and M. Arceci for technical assistance. This work was supported by A.I.R.C. (IG 17352) and “Progetti Ateneo” Sapienza University of Rome to A.F.; and ERC-2013 (AdG 340172–MUNCODD), Epigen-Epigenomics Flagship Project, AFM-Telethon (17835), PRIN 2013, AriSLA full grant 2014 “ARCI” and HFSP (RGP0009/2014) to I.B. Contribution of AIRC (StG 4841) and FILAS-RU-2014-1020 to FF was greatly appreciated.en
dc.publisherImpact Journals, LLCen
dc.relation.urlhttp://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=11165en
dc.rightsArchived with thanks to Impact Journals, LLC. The article is distributed under the terms of the Creative Commons Attribution 3.0 License.en
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/en
dc.subjectlong non-coding RNAen
dc.subjectmiR-125en
dc.subjectacute myeloid leukemiaen
dc.subjectIRF4en
dc.titleThe miR-223 host non-coding transcript linc-223 induces IRF4 expression in acute myeloid leukemia by acting as a competing endogenous RNAen
dc.typeArticleen
dc.contributor.departmentKAUST Environmental Epigenetics Research Program (KEEP)en
dc.identifier.journalOncotargeten
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionDepartment of Biology and Biotechnology “C. Darwiny”, Sapienza University of Rome, Rome, 00185, Italyen
dc.contributor.institutionDepartment of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome, 00185, Italyen
dc.contributor.institutionCenter for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Rome, 00161, Italyen
dc.contributor.institutionInstitute Pasteur Fondazione Cenci-Bolognetti, Sapienza University of Rome, Rome, 00185, Italyen
kaust.authorMangiavacchi, Ariannaen
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