Abstract
To investigate the relative expression of miRNA 17-5p and one of its target genes E2F1 in peripheral blood of systemic lupus erythematosus SLE pediatric patients. miRNA 17-5p and its target E2F1 miRNA expressions in SLE peripheral blood and controls were analyzed by TaqMan real-time qPCR. Peripheral blood mononuclear cells (PBMCs) of SLE and controls were transfected using a nucleofector device, and E2F1 protein expression was analyzed using luciferase reporter gene assays. Results showed significant downregulation of miRNA 17-5p in SLE patients compared to healthy controls; moreover, miRNA 17-5p was more downregulated in patients on no treatment compared to those on treatment. Relative expression of E2F1, which is target for miRNA 17-5p, was significantly downregulated as well on both miRNA and protein levels in SLE. Our data show an unexpected dual downregulation of both miRNA 17-5p and its target gene E2F1 on the mRNA and protein levels. This may suggest an expression pattern of miRNA 17-5p and its target E2F1 that may be specific to SLE.
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References
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297
Dai Y et al (2007) Microarray analysis of microRNA expression in peripheral blood cells of systemic lupus erythematosus patients. Lupus 16(12):939–946
Dai Y et al (2009) Comprehensive analysis of microRNA expression patterns in renal biopsies of lupus nephritis patients. Rheumatol Int 29(7):749–754
Pauley KM, Cha S, Chan EK (2009) MicroRNA in autoimmunity and autoimmune diseases. J Autoimmun 32(3–4):189–194
Tang Y et al (2009) MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins. Arthr Rheumatol 60(4):1065–1075
Zhao X et al (2010) MicroRNA-125a contributes to elevated inflammatory chemokine RANTES via targeting KLF13 in systemic lupus erythematosus. Arthr Rheumol
Lashine YA et al (2011) Expression signature of microRNA-181-a reveals its crucial role in the pathogenesis of paediatric systemic lupus erythematosus. Clin Exp Rheumatol 29(2): 351–357
Mendell JT (2008) MiRiad roles for the miR-17-92 cluster in development and disease. Cell 133(2):217–222
Cloonan N et al (2008) The miR-17-5p microRNA is a key regulator of the G1/S phase cell cycle transition. Genome Biol 9(8):R127
O’Donnell KA et al (2005) C-Myc-regulated microRNAs modulate E2F1 expression. Nature 435(7043):839–843
Trompeter HI et al (2011) MicroRNAs MiR-17, MiR-20a, and MiR-106b act in concert to modulate E2F activity on cell cycle arrest during neuronal lineage differentiation of USSC. PLoS One 6(1): e16138
DeGregori J, Johnson DG (2006) Distinct and overlapping roles for E2F family members in transcription, proliferation and apoptosis. Curr Mol Med 6(7):739–748
Attwooll C, LazzeriniDenchi E, Helin K (2004) The E2F family: specific functions and overlapping interests. EMBO J 23(24):4709–4716
Panchanathan R, Xin H, Choubey D (2008) Disruption of mutually negative regulatory feedback loop between interferon-inducible p 202 protein and the E2F family of transcription factors in lupus-prone mice. J Immunol 180(9):5927–5934
Woods K, Thomson JM, Hammond SM (2007) Direct regulation of an oncogenic micro-RNA cluster by E2F transcription factors. J Biol Chem 282(4):2130–2134
Aguda BD et al (2008) MicroRNA regulation of a cancer network: consequences of the feedback loops involving miR-17-92, E2F, and Myc. Proc Natl Acad Sci U S A 105(50):19678–19683
Chow TF et al (2010) The miR-17-92 cluster is over expressed in and has an oncogenic effect on renal cell carcinoma. J Urol 183(2):743–751
Levati L et al (2009) Altered expression of selected microRNAs in melanoma: antiproliferative and proapoptotic activity of miRNA-155. Int J Oncol 35(2):393–400
Tsujiura M et al (2010) Circulating microRNAs in plasma of patients with gastric cancers. Br J Cancer 102(7):1174–1179
Mortarino M et al (2010) Identification of suitable endogenous controls and differentially expressed microRNAs in canine fresh-frozen and FFPE lymphoma samples. Leuk Res 34(8):1070–1077
Li H et al (2010) miR-17-5p promotes human breast cancer cell migration and invasion through suppression of HBP1. Breast Cancer Res Treat
Cox MB et al (2010) MicroRNAs miR-17 and miR-20a inhibit T cell activation genes and are under-expressed in MS whole blood. PLoS One 5(8): e12132
Lindberg RL et al (2010) Altered expression of miR-17-5p in CD4+ lymphocytes of relapsing-remitting multiple sclerosis patients. Eur J Immunol 40(3): 888–898
Krek A et al (2005) Combinatorial microRNA target predictions. Nat Genet 37(5):495–500
Garcia I et al (2000) A role for E2F1 in the induction of apoptosis during thymic negative selection. Cell Growth Differ 11(2):91–98
Salam MA et al (2004) E2f1 mutation induces early onset of diabetes and Sjogren’s syndrome in nonobese diabetic mice. J Immunol 173(8):4908–4918
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We acknowledge the SLE pediatric patients and the healthy controls.
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Aboelenein, H.R.A., Salah, S., Lashine, Y.A. et al. Dual downregulation of microRNA 17-5p and E2F1 transcriptional factor in pediatric systemic lupus erythematosus patients. Rheumatol Int 33, 1333–1338 (2013). https://doi.org/10.1007/s00296-012-2543-9
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DOI: https://doi.org/10.1007/s00296-012-2543-9