MicroRNA Expression Signature in Degenerative Aortic Stenosis

Abstract

Degenerative aortic stenosis, characterized by narrowing of the exit of the left ventricle of the heart, has become the most common valvular heart disease in the elderly. The aim of this study was to investigate the microRNA (miRNA) signature in degenerative AS. Through microarray analysis, we identified the miRNA expression signature in the tissue samples from healthy individuals (n = 4) and patients with degenerative AS (n = 4). Six miRNAs (hsa-miR-193a-3p, hsa-miR-29b-1-5p, hsa-miR-505-5p, hsa-miR-194-5p, hsa-miR-99b-3p, and hsa-miR-200b-3p) were overexpressed and 14 (hsa-miR-3663-3p, hsa-miR-513a-5p, hsa-miR-146b-5p, hsa-miR-1972, hsa-miR-718, hsa-miR-3138, hsa-miR-21-5p, hsa-miR-630, hsa-miR-575, hsa-miR-301a-3p, hsa-miR-636, hsa-miR-34a-3p, hsa-miR-21-3p, and hsa-miR-516a-5p) were downregulated in aortic tissue from AS patients. GeneSpring 13.1 was used to identify potential human miRNA target genes by comparing a 3-way comparison of predictions from TargetScan, PITA, and microRNAorg databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to identify potential pathways and functional annotations associated with AS. Twenty miRNAs were significantly differentially expressed between patients with AS samples and normal controls and identified potential miRNA targets and molecular pathways associated with this morbidity. This study describes the miRNA expression signature in degenerative AS and provides an improved understanding of the molecular pathobiology of this disease.

Integrative Multi-Omics Analysis in Calcific Aortic Valve Disease Reveals a Link to the Formation of Amyloid-Like Deposits

“…The initial search yielded 196 unique records for miRNA transcriptomics, 482 for mRNA transcriptomics and 93 for proteomics in CAVD. After applying the inclusion and exclusion criteria, 5 miRNA transcriptomics [ 18 , 19 , 20 , 21 , 22 ], 5 mRNA transcriptomics [ 15 , 20 , 23 , 24 , 25 ] and 10 proteomics [ 15 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ] records were eligible for the subsequent analyses ( Figure 1 A, Supplementary Figure S1, Supplementary Tables S1–S3 ). We identified only one single metabolomics study, which was only considered for integration analysis.…”

miR-636: A Newly-Identified Actor for the Regulation of Pulmonary Inflammation in Cystic Fibrosis

“…The first articles reporting the dysregulation of miR-636 expression were published in 2011 (21, 22). To our knowledge, in most studies from 2011 to the present day, only miR-636 expression dysregulation has been identified in various pathological contexts, such as myelodysplastic syndrome (21), osteoporosis fractures (23), aortic stenosis (24), dilated cardiomyopathy (25), colorectal tumour (26), colon adenocarcinoma (27), urothelial carcinoma in chronic haemodialysis patients (28), diabetic nephropathy (29), and breast cancer (30), but there have been no such observations regarding CF. Furthermore, only one study has reported a direct link between this miRNA and one of the predicted targets at the 3′-UTR region of GRα (22).…”

A miR-29b Byproduct Sequence Exhibits Potent Tumor-Suppressive Activities via Inhibition of NF-κB Signaling in KRAS-Mutant Colon Cancer Cells

“…For example, miR-29b-1-5p is described as miR-29b à on 3D-Gene Human miRNA Oligo chips (Toray Industries), which means it is degraded and has no apparent human physiologic function (38). Indeed, a number of studies >500 on PubMed database focused on miR-29b-3p, whereas there are only 6 reports on miR-29b-1-5p (27,28,(40)(41)(42)(43). We also confirmed that expression levels of miR-29b-1-5p were very low in clinical colorectal cancer tumor samples, which contrasts to high expression of miR-29b-3p using the same colorectal cancer samples.…”