title: miRNA-548c: a specific signature in circulating PBMCs from dilated cardiomyopathy patients.
abstract: High fidelity genome-wide expression analysis has strengthened the idea that microRNA (miRNA) signatures in peripheral blood mononuclear cells (PBMCs) can be potentially used to predict the pathology when anatomical samples are inaccessible like the heart. PBMCs from 48 non-failing controls and 44 patients with relatively stable chronic heart failure (ejection fraction of ≤ 40%) associated with dilated cardiomyopathy (DCM) were used for miRNA analysis. Genome-wide miRNA-microarray on PBMCs from chronic heart failure patients identified miRNA signature uniquely characterized by the downregulation of miRNA-548 family members. We have also independently validated downregulation of miRNA-548 family members (miRNA-548c & 548i) using real time-PCR in a large cohort of independent patient samples. Independent in silico Ingenuity Pathway Analysis (IPA) of miRNA-548 targets shows unique enrichment of signaling molecules and pathways associated with cardiovascular disease and hypertrophy. Consistent with specificity of miRNA changes with pathology, PBMCs from breast cancer patients showed no alterations in miRNA-548c expression compared to healthy controls. These studies suggest that miRNA-548 family signature in PBMCs can therefore be used to detect early heart failure. Our studies show that cognate networking of predicted miRNA-548 targets in heart failure can be used as a powerful ancillary tool to predict the ongoing pathology.
authors.affiliation: Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, USA.
authors.forename: Manveen K
authors.initials: MK
authors.lastname: Gupta
authors.forename: Carmel
authors.initials: C
authors.lastname: Halley
authors.forename: Zhong-Hui
authors.initials: ZH
authors.lastname: Duan
authors.forename: Jason
authors.initials: J
authors.lastname: Lappe
authors.forename: Jamie
authors.initials: J
authors.lastname: Viterna
authors.forename: Subhra
authors.initials: S
authors.lastname: Jana
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Augoff
authors.forename: Maradumane L
authors.initials: ML
authors.lastname: Mohan
authors.forename: Neelakantan T
authors.initials: NT
authors.lastname: Vasudevan
authors.forename: Jie
authors.initials: J
authors.lastname: Na
authors.forename: Khalid
authors.initials: K
authors.lastname: Sossey-Alaoui
authors.forename: Xiuping
authors.initials: X
authors.lastname: Liu
authors.forename: Chang-Gong
authors.initials: CG
authors.lastname: Liu
authors.forename: W H Wilson
authors.initials: WH
authors.lastname: Tang
authors.forename: Sathyamangla V
authors.initials: SV
authors.lastname: Naga Prasad
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D006333:Heart Failure / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged
chemical_list: D035683:MicroRNAs
keywords: Biomarker; Canonical signaling networks; Dilated cardiomyopathy; Peripheral blood mononuclear cells (PBMC); microRNA-548