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: Arianna Mangiavacchi, Melissa Sorci, Silvia Masciarelli, Simone Larivera, Ivano Legnini, Ilaria Iosue, Irene Bozzoni, Francesco Fazi, Alessandro Fatica
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 37 Pg. 60155-60168 (Sep 13 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27517498 (Publication Type: Journal Article)

Chemical References

• Interferon Regulatory Factors
• MIRN125 microRNA, human
• MIRN223 microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• interferon regulatory factor-4

Topics

• Adult
• Aged
• Cell Differentiation (genetics)
• Female
• Gene Expression Profiling (methods)
• Gene Expression Regulation, Leukemic
• HL-60 Cells
• Humans
• Interferon Regulatory Factors (genetics, metabolism)
• K562 Cells
• Leukemia, Myeloid, Acute (genetics, metabolism, pathology)
• Male
• MicroRNAs (genetics, metabolism)
• Middle Aged
• RNA, Long Noncoding (genetics)
• Young Adult