| 词条 | Mir-223 |
| 释义 |
| Name = mir-223 | image = MiR-223 secondary structure.png | width = 220px | caption = miR-223 microRNA secondary structure and sequence conservation | Symbol = mir-223 | AltSymbols = | Rfam = RF00664 | miRBase_family = MIPF0000067 | RNA_type = microRNA | Tax_domain = Eukaryota; Euteleostomi | EntrezGene = 407008 | HGNCid = 31603 | OMIM = 300694 }} In molecular biology MicroRNA-223 (miR-223) is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms. miR-223 is a hematopoietic specific microRNA with crucial functions in myeloid lineage development.[1][2] It plays an essential role in promoting granulocytic differentiation [2][3] while also being associated with the suppression of erythrocytic differentiation.[4] miR-223 is commonly repressed in hepatocellular carcinoma [5] and leukemia.[6][7][8][9] Higher expression levels of miRNA-223 are associated with extranodal marginal-zone lymphoma of mucosa-associated lymphoid tissue of the stomach [10] and recurrent ovarian cancer.[11] In some cancers the microRNA-223 down-regulation is correlated with higher tumor burden, disease aggressiveness, and poor prognostic factors.[7] MicroRNA-223 is also associated with rheumatoid arthritis,[12] sepsis,[13] type 2 diabetes,[14] and hepatic ischemia.[15] CharacterizationMicroRNA-223 was initially identified bioinformatically and it was subsequently characterized as part of the haematopoietic system.[2] Its gene resembles a myeloid gene and it could be driven by the PU.1 and C/EBPα proteins which are myeloid transcription factors.[16] MicroRNA-223 selectively targets distinct populations of transcripts harboring AU-rich elements. More specifically, it was validated that the RhoB mRNA is a bona fide miR-223 target.[17] miR-223 also regulates cyclin E activity by modulating expression of the FBXW7 protein. In particular, overexpression of miR-223 reduces FBXW7 mRNA levels while increasing endogenous cyclin E protein and activity levels.[18] Role in hematopoiesisThe role of miR-223 in hematopoiesis has been extensively analyzed in the past few years. During granulopoiesis miR-223 acts as fine-tuner of granulocytic differentiation, maturation, and function.[19] More specifically, human granulocytic differentiation is controlled by a regulatory circuitry involving miR-223 and two transcriptional factors, NFIA and C/EBPα. These two factors compete for binding: NFI-A maintains miR-223 at low levels whereas C/EBPα upregulates miR-223 expression. The competition by C/EBPα and the granulocytic differentiation are favored by a negative-feedback loop in which miR-223 represses NFI-A translation.[20] Analysis of expression profiles indicate that miR-223 expression decreases as cells mature during monocytic, erythroid, and mast cell differentiation.[2][19] miR-223 down-regulation during erythropoiesis is required for erythrocyte proliferation and differentiation at progenitor and precursor level.[19] This down-modulation promotes erythropoiesis favoring translation of the key functional protein LMO2 resulting in reversible regulation of erythroid and megakaryocytic differentiation.[4] MicroRNA-223 also plays an essential role during osteoclast differentiation. More specifically, miR-223 expression suppresses the differentiation of osteoclast precursors into osteoclast thus making it a potential viable therapeutic target for a range of bone metabolic disorders with excess osteoclast activity.[21] Involvement in diseaseCancerMicroRNA-223 is commonly repressed in hepatocellular carcinoma,[5] chronic lymphocytic leukemia,[7] acute lymphoblastic leukemia,[8] acute myeloid leukemia,[6][9] gastric MALT lymphoma,[10] and recurrent ovarian cancer.[11] Integrative analysis in hepatocellular carcinoma implicates Stathmin 1 (STMN1) as a downstream target of miR-223. Furthermore, miR-223 could suppress the luciferase activity in reporter construct containing the STMN1 3' untranslated region.[5] The reduced expressions of miR-223 may predispose to the development of hepatocellular carcinoma via the widespread induction of chromosomal instability by STMN1.[5] MicroRNA-223 blocks the translation of E2F1 leading to inhibition of cell-cycle progression followed by myeloid differentiation.[9] In acute myeloid leukemia (AML), miR-223 is down-regulated thus leading to E2F1 overexpression. The overexpressed E2F1 could bind to the miR-223 promoter and in turn lead to a further decrease in miR-223 expression through a negative feedback loop followed by myeloid cell-cycle progression at the expense of differentiation.[6] Overexpression of E2F1 has been shown to be an oncogenic event that predisposes cells to transformation. While there is some indication of the miR-223 role in AML there is still little known about this microRNA function in chronic lymphocytic and acute lymphoblastic leukemia. Nevertheless, MicroRNA-223 expression levels decreased significantly with the progression of these two diseases thus associating miR-223 down-regulation with higher tumor burden, disease aggressiveness, and poor prognostic factors.[7][8] Gastric MALT lymphoma and recurrent ovarian cancer are associated with higher levels of MicroRNA-223 expression [10][11] making them a potential biomarker. Rheumatoid arthritisMicroRNA-223 is overexpressed in the T-lymphocytes cells of rheumatoid arthritis patients suggesting that its expression in this cell type could contribute to the etiology of the disease.[12] SepsisThere is some evidence that MicroRNA-223 and MicroRNA-146a are significantly reduced in septic patients compared with systemic inflammatory response syndrome (SIRS) patients and/or healthy controls.[13] This suggests that miR-223 can be used as a biomarker for distinguishing sepsis from SIRS. DiabetesQuantitative miRNA expression analyses revealed that miR-223 was consistently upregulated in the insulin-resistant hearts of patients with type 2 diabetes. This effect was associated with miR-223 role in Glut4 regulation and glucose metabolism.[14] Hepatic ischemiaA recent study concluded that hepatic ischemia/reperfusion injury might be another form of liver disease that is associated with the alteration in miR-223 expression.[15] Correlation analysis revealed that hepatic miR-223 expression levels are significantly positively correlated with the serum markers of hepatic ischemia. Further, prediction assay of miRNA targets mRNA, acyl-CoA synthetase long-chain family member 3, ephrin A1, and ras homolog gene family member B were predicted to be downstream targets of miR-223. See also
References1. ^{{cite journal |vauthors=Sun W, Shen W, Yang S, Hu F, Li H, Zhu TH |title=miR-223 and miR-142 attenuate hematopoietic cell proliferation, and miR-223 positively regulates miR-142 through LMO2 isoforms and CEBP-β. |journal=Cell Res |volume=20 |issue=10 |pages=1158–69 |year=2010 |pmid=20856265 |doi=10.1038/cr.2010.134}} 2. ^1 2 3 {{cite journal |vauthors=Johnnidis JB, Harris MH, Wheeler RT, Stehling-Sun S, Lam MH, Kirak O, Brummelkamp TR, Fleming MD, Camargo FD |title=Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. |journal=Nature |volume=451 |issue=7182 |pages=1125–9 |year=2008 |pmid=18278031 |doi=10.1038/nature06607}} 3. ^{{cite journal |vauthors=Fazi F, Racanicchi S, Zardo G, Starnes LM, Mancini M, Travaglini L, Diverio D, Ammatuna E, Cimino G, Lo-Coco F, Grignani F, Nervi C |title=Epigenetic silencing of the myelopoiesis regulator microRNA-223 by the AML1/ETO oncoprotein. |journal=Cancer Cell |volume=12 |issue=5 |pages=457–66 |year=2007 |pmid=17996649 |doi=10.1016/j.ccr.2007.09.020}} 4. ^1 {{cite journal |vauthors=Yuan JY, Wang F, Yu J, Yang GH, Liu XL, Zhang JW |title=MicroRNA-223 reversibly regulates erythroid and megakaryocytic differentiation of K562 cells |journal=J Cell Mol Med |volume=13 |issue=11–12 |pages=4551–9 |year= 2009|pmid=19017354 |pmc=4515070 |doi=10.1111/j.1582-4934.2008.00585.x}} 5. ^1 2 3 {{cite journal |vauthors=Wong QW, Lung RW, Law PT, Lai PB, Chan KY, To KF, Wong N |title=MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of Stathmin1 |journal=Gastroenterology |volume=135 |issue=1 |pages=257–69 |year=2008 |pmid=18555017 |doi=10.1053/j.gastro.2008.04.003}} 6. ^1 2 {{cite journal |vauthors=Eyholzer M, Schmid S, Schardt JA, Haefliger S, Mueller BU, Pabst T |title=Complexity of miR-223 regulation by CEBPA in human AML |journal=Leuk Res |volume=34 |issue=5 |pages=672–6 |year=2010 |pmid=20018373 |doi=10.1016/j.leukres.2009.11.019}} 7. ^1 2 3 {{cite journal |vauthors=Stamatopoulos B, Meuleman N, Haibe-Kains B, Saussoy P, Van Den Neste E, Michaux L, Heimann P, Martiat P, Bron D, Lagneaux L |title=microRNA-29c and microRNA-223 down-regulation has in vivo significance in chronic lymphocytic leukemia and improves disease risk stratification |journal=Blood |volume=113 |issue=21 |pages=5237–45 |year=2009 |pmid=19144983 |doi=10.1182/blood-2008-11-189407}} 8. ^1 2 {{cite journal |vauthors=Chiaretti S, Messina M, Tavolaro S, Zardo G, Elia L, Vitale A, Fatica A, Gorello P, Piciocchi A, Scappucci G, Bozzoni I, Fozza C, Candoni A, Guarini A, Foà R |title=Gene expression profiling identifies a subset of adult T-cell acute lymphoblastic leukemia with myeloid-like gene features and over-expression of miR-223 |journal=Haematologica |volume=95 |issue=7 |pages=1114–21 |year=2010 |pmid=20418243 |doi=10.3324/haematol.2009.015099 |pmc=2895035}} 9. ^1 2 {{cite journal |vauthors=Pulikkan JA, Dengler V, Peramangalam PS, Peer Zada AA, Müller-Tidow C, Bohlander SK, Tenen DG, Behre G |title=Cell-cycle regulator E2F1 and microRNA-223 comprise an autoregulatory negative feedback loop in acute myeloid leukemia |journal=Blood |volume=115 |issue=9 |pages=1768–78 |year=2010|pmid=20029046 |doi=10.1182/blood-2009-08-240101 |pmc=2832809}} 10. ^1 2 {{cite journal |vauthors=Liu TY, Chen SU, Kuo SH, Cheng AL, Lin CW |title=E2A-positive gastric MALT lymphoma has weaker plasmacytoid infiltrates and stronger expression of the memory B-cell-associated miR-223: possible correlation with stage and treatment response |journal=Mod Pathol |volume= 23|issue= 11|pages= 1507–17|year=2010 |pmid=20802470 |doi=10.1038/modpathol.2010.139}} 11. ^1 2 {{cite journal |vauthors=Laios A, O'Toole S, Flavin R, Martin C, Kelly L, Ring M, Finn SP, Barrett C, Loda M, Gleeson N, D'Arcy T, McGuinness E, Sheils O, Sheppard B, O' Leary J |title=Potential role of miR-9 and miR-223 in recurrent ovarian cancer |journal=Mol Cancer |volume=7 |issue= |pages=35 |year=2008 |pmid=18442408 |doi=10.1186/1476-4598-7-35 |pmc=2383925}} 12. ^1 {{cite journal |vauthors=Fulci V, Scappucci G, Sebastiani GD, Giannitti C, Franceschini D, Meloni F, Colombo T, Citarella F, Barnaba V, Minisola G, Galeazzi M, Macino G |title=miR-223 is overexpressed in T-lymphocytes of patients affected by rheumatoid arthritis |journal=Hum Immunol |volume=71 |issue=2 |pages=206–11 |year=2010 |pmid=19931339 |doi=10.1016/j.humimm.2009.11.008}} 13. ^1 {{cite journal |vauthors=Wang JF, Yu ML, Yu G, Bian JJ, Deng XM, Wan XJ, Zhu KM |title=Serum miR-146a and miR-223 as potential new biomarkers for sepsis |journal=Biochem Biophys Res Commun |volume=394 |issue=1 |pages=184–8 |year=2010 |pmid=20188071 |doi=10.1016/j.bbrc.2010.02.145}} 14. ^1 {{cite journal |author1=Lu Han |author2=Buchan Rachel |author3=Cook Stuart |title= MicroRNA-223 regulates Glut4 expression and cardiomyocyte glucose metabolism |journal=Cardiovasc Res |volume=86 |issue=3 |pages=410–420 |year=2010 |pmid=20080987 |doi=10.1093/cvr/cvq010}} 15. ^1 {{cite journal |vauthors=Yu CH, Xu CF, Li YM |title=Association of MicroRNA-223 expression with hepatic ischemia/reperfusion injury in mice |journal=Dig Dis Sci |volume=54 |issue=11 |pages=2362–6 |year=2009 |pmid=19104939 |doi=10.1007/s10620-008-0629-8}} 16. ^{{cite journal |vauthors=Fukao T, Fukuda Y, Kiga K, Sharif J, Hino K, Enomoto Y, Kawamura A, Nakamura K, Takeuchi T, Tanabe M |title=An evolutionarily conserved mechanism for microRNA-223 expression revealed by microRNA gene profiling |journal=Cell |volume=129 |issue=3 |pages=617–31 |year=2007 |pmid=17482553 |doi=10.1016/j.cell.2007.02.048}} 17. ^{{cite journal |vauthors=Sun G, Li H, Rossi JJ |title=Sequence context outside the target region influences the effectiveness of miR-223 target sites in the RhoB 3'UTR |journal=Nucleic Acids Res |volume=38 |issue=1 |pages=239–52 |year=2010 |pmid=19850724 |doi=10.1093/nar/gkp870 |pmc=2800228}} 18. ^{{cite journal |vauthors=Xu Y, Sengupta T, Kukreja L, Minella AC |title=MicroRNA-223 regulates cyclin E activity by modulating expression of F-box and WD-40 domain protein 7 |journal=J Biol Chem |volume= 285|issue= 45|pages= 34439–46|year=2010 |pmid=20826802 |doi=10.1074/jbc.M110.152306 |pmc=2966058}} 19. ^1 2 {{cite journal |vauthors=Felli N, Pedini F, Romania P, Biffoni M, Morsilli O, Castelli G, Santoro S, Chicarella S, Sorrentino A, Peschle C, Marziali G |title=MicroRNA 223-dependent expression of LMO2 regulates normal erythropoiesis |journal=Haematologica |volume=94 |issue=4 |pages=479–86 |year=2009 |pmid=19278969 |doi=10.3324/haematol.2008.002345 |pmc=2663611}} 20. ^{{cite journal |vauthors=Fazi F, Rosa A, Fatica A, Gelmetti V, De Marchis ML, Nervi C, Bozzoni I |title=A minicircuitry {{sic|comprised |hide=y|of}} microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis |journal=Cell |volume=123 |issue=5 |pages=819–31 |year=2005 |pmid=16325577 |doi=10.1016/j.cell.2005.09.023}} 21. ^{{cite journal |vauthors=Sugatani T, Hruska KA |title=MicroRNA-223 is a key factor in osteoclast differentiation |journal=J Cell Biochem |volume=101 |issue=4 |pages=996–9 |year=2007 |pmid=17471500 |doi=10.1002/jcb.21335}} Further reading
External links
1 : MicroRNA |
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