scholarly journals MON-100 Unique miRNA Signature in HIV Lipodystrophy with Reduced Adipose Dicer Expression

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Suman Srinivasa ◽  
Ruben Garcia ◽  
Martin Torriani ◽  
Kathleen Fitch ◽  
Patrick Maehler ◽  
...  
Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 164-LB
Author(s):  
SOUMYALEKSHMI NAIR ◽  
VALESKA ORMAZABAL ◽  
NANTHINI JAYABALAN ◽  
DOMINIC GUANZON ◽  
ANDREW LAI ◽  
...  

2009 ◽  
pp. n/a-n/a ◽  
Author(s):  
Areeg Faggad ◽  
Jan Budczies ◽  
Oleg Tchernitsa ◽  
Silvia Darb-Esfahani ◽  
Jalid Sehouli ◽  
...  

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Siqi Bao ◽  
Ting Hu ◽  
Jiaqi Liu ◽  
Jianzhong Su ◽  
Jie Sun ◽  
...  

Abstract Background Breast cancer (BC) is the most frequently diagnosed cancer and the leading cause of cancer-associated deaths in women. Recent studies have indicated that microRNA (miRNA) regulation in genomic instability (GI) is associated with disease risk and clinical outcome. Herein, we aimed to identify the GI-derived miRNA signature in extracellular vesicles (EVs) as a minimally invasive biomarker for early diagnosis and prognostic risk stratification. Experimental design Integrative analysis of miRNA expression and somatic mutation profiles was performed to identify GI-associated miRNAs. Then, we constructed a discovery and validation study with multicenter prospective cohorts. The GI-derived miRNA signature (miGISig) was developed in the TCGA discovery cohort (n = 261), and was subsequently independently validated in internal TCGA validation (n = 261) and GSE22220 (n = 210) cohorts for prognosis prediction, and in GSE73002 (n = 3966), GSE41922 (n = 54), and in-house clinical exosome (n = 30) cohorts for diagnostic performance. Results We identified a GI-derived three miRNA signature (MIR421, MIR128-1 and MIR128-2) in the serum extracellular vesicles of BC patients, which was significantly associated with poor prognosis in all the cohorts tested and remained as an independent prognostic factor using multivariate analyses. When integrated with the clinical characteristics, the composite miRNA-clinical prognostic indicator showed improved prognostic performance. The miGISig also showed high accuracy in differentiating BC from healthy controls with the area under the receiver operating characteristics curve (ROC) with 0.915, 0.794 and 0.772 in GSE73002, GSE41922 and TCGA cohorts, respectively. Furthermore, circulating EVs from BC patients in the in-house cohort harbored elevated levels of miGISig, with effective diagnostic accuracy. Conclusions We report a novel GI-derived three miRNA signature in EVs, as an excellent minimally invasive biomarker for the early diagnosis and unfavorable prognosis in BC.


Author(s):  
Junyu Cao ◽  
Liankang Sun ◽  
Jie Li ◽  
Cancan Zhou ◽  
Liang Cheng ◽  
...  
Keyword(s):  
Rna Seq ◽  

2020 ◽  
Vol 152 ◽  
pp. S169-S170
Author(s):  
K. Unger ◽  
D.F. Fleischmann ◽  
V. Ruf ◽  
J. Felsberg ◽  
D. Piehlmaier ◽  
...  

2004 ◽  
Vol 140 (10) ◽  
pp. 786 ◽  
Author(s):  
Colleen Hadigan ◽  
Sigal Yawetz ◽  
Abraham Thomas ◽  
Fiona Havers ◽  
Paul E. Sax ◽  
...  

2008 ◽  
Vol 295 (6) ◽  
pp. H2512-H2521 ◽  
Author(s):  
Satoshi Asada ◽  
Tomosaburo Takahashi ◽  
Koji Isodono ◽  
Atsuo Adachi ◽  
Hiroko Imoto ◽  
...  

Although the modulated expression of Dicer is documented upon neoplastic transformation, little is known of the regulation of Dicer expression by environmental stimuli and its roles in the regulation of cellular functions in primary cells. In this study, we found that Dicer expression was downregulated upon serum withdrawal in human umbilical vein endothelial cells (HUVECs). Serum withdrawal induced a time-dependent repression of Dicer expression, which was specifically rescued by vascular endothelial cell growth factor or sphingosine-1-phosphate. When Dicer expression was silenced by short-hairpin RNA against Dicer, the cells were more prone to apoptosis under serum withdrawal, whereas the rate of apoptosis was comparable with control cells in the serum-containing condition. Real-time PCR-based gene expression profiling identified several genes, the expression of which was modulated by Dicer silencing, including adhesion and matrix-related molecules, caspase-3, and nitric oxide synthase 3 (NOS3). Dicer silencing markedly impaired migratory functions without affecting cell adhesion and repressed phosphorylation of focal adhesion kinase and proline-rich tyrosine kinase 2 in adherent HUVECs. Dicer knockdown upregulated caspase-3 and downregulated NOS3 expression, and serum withdrawal indeed increased caspase-3 and decreased NOS3 expression. Furthermore, the overexpression of Dicer in HUVECs resulted in a marked reduction in apoptosis upon serum withdrawal and a decreased caspase-3 and increased NOS3 expression. The inhibition of NOS activity by Nω-nitro-l-arginine methyl ester abrogated the effect of Dicer overexpression to rescue the cells from serum withdrawal-induced apoptosis. These results indicated that serum withdrawal decreases Dicer expression, leading to an increased susceptibility to apoptosis through the regulation of caspase-3 and NOS3 expression.


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