MicroRNA deep sequencing reveals chamber-specific miR-208 family expression patterns in the human heart

Kakimoto, Yu; Tanaka, Masayuki; Kanazawa, Hiroshi; Hayashi, Hideki; Ochiai, Eriko; Osawa, Motoki

doi:10.1016/j.ijcard.2016.02.145

Cited by 43 publications

(35 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent data report differentiated dysregulations of miRNAs in right ventricular (RV) heart failure (RVHF) compared to left ventricular (LV) heart failure (LVHF) [72,73], exploring a potential way to develop the first RV-specific HF therapies [74]. The differentiated applicability of miRNAs in anatomically separated structures of the heart is underlined by recent data revealing chamber-specific expression of miR-208 and their host genes α-MHC and β-MHC (see above) in the human heart [75]. From this point of view, the application of miRNAs could allow for differentiated diagnostic purposes in separate types of heart disease.…”

Section: Mirnas In Heart Failurementioning

confidence: 99%

microRNAs in cardiovascular disease – clinical application

Schulte

Karakas

Zeller

2017

Clinical Chemistry and Laboratory Medicine (CCLM)

104

View full text Add to dashboard Cite

microRNAs (miRNAs) are well-known, powerful regulators of gene expression, and their potential to serve as circulating biomarkers is widely accepted. In cardiovascular disease (CVD), numerous studies have suggested miRNAs as strong circulating biomarkers with high diagnostic as well as prognostic power. In coronary artery disease (CAD) and heart failure (HF), miRNAs have been suggested as reliable biomarkers matching up to established protein-based such as cardiac troponins (cT) or natriuretic peptides. Also, in other CVD entities, miRNAs were identified as surprisingly specific biomarkers -with great potential for clinical applicability, especially in those entities that lack specific protein-based biomarkers such as atrial fibrillation (AF) and acute pulmonary embolism (APE). In this regard, miRNA signatures, comprising a set of miRNAs, yield high sensitivity and specificity. Attempts to utilize miRNAs as therapeutic agents have led to promising results. In this article, we review the clinical applicability of circulating miRNAs in CVD. We are giving an overview of miRNAs as biomarkers in numerous CVD entities to depict the variety of their potential clinical deployment. We illustrate the function of miRNAs by means of single miRNA examples in CVD.

show abstract

Section: Mirnas In Heart Failurementioning

confidence: 99%

microRNAs in cardiovascular disease – clinical application

Schulte

Karakas

Zeller

2017

Clinical Chemistry and Laboratory Medicine (CCLM)

104

View full text Add to dashboard Cite

show abstract

“…Toward an even more comprehensive picture of miRNA expression in human tissues, it will also be helpful to record different miRNA pattern within tissues especially form rather heterogeneous tissues as reported by Kakimoto and coworkers for a chamber specific expression of the afore-mentioned miR-208a-3p. 21 With respect to body fluids, our data collection contains a variety of diseases and control samples. As for these body fluids there is a fundamental problem in obtaining several of these samples from the same individual and to compare these data with the data obtained form tissues of the corpses.…”

Section: Limitations and Future Directionsmentioning

confidence: 99%

Distribution of microRNA biomarker candidates in solid tissues and body fluids

et al. 2016

View full text Add to dashboard Cite

Small non-coding RNAs, especially microRNAs, are discussed as promising biomarkers for a substantial number of human pathologies. A broad understanding in which solid tissues, cell types or body fluids a microRNA is expressed helps also to understand and to improve the suitability of miRNAs as non-or minimally-invasive disease markers. We recently reported the Human miRNA Tissue Atlas (http://www.ccb.uni-saarland.de/tissueatlas) containing 105 miRNA profiles of 31 organs from 2 corpses. We subsequently added miRNA profiles measured by others and us using the same array technology as for the first version of the Human miRNA Tissue Atlas. The latter profiles stem from 163 solid organs including lung, prostate and gastric tissue, from 253 whole blood samples and 66 fractioned blood cell isolates, from body fluids including 72 serum samples, 278 plasma samples, 29 urine samples, and 16 saliva samples and from different collection and storage conditions. While most miRNAs are ubiquitous abundant in solid tissues and whole blood, we also identified miRNAs that are rather specific for tissues. Our web-based repository now hosting 982 full miRNomes all of which are measured by the same microarray technology. The knowledge of these variant abundances of miRNAs in solid tissues, in whole blood and in other body fluids is essential to judge the value of miRNAs as biomarker.

show abstract

“…Based on these results, miR-3546 was selected to further determine its effect on sublytic C5b-9-triggered GMC apoptosis and the related regulatory mechanism. Notably, miR-3546 belongs to miR-208 family, and though several documents have pointed out that miR-208 has regulatory role in myocardial injury [42][43][44], there has not been any report about the function of miR-3546.…”

Section: Discussionmentioning

confidence: 99%

Sublytic C5b-9 Induces Glomerular Mesangial Cell Apoptosis Through miR-3546/SOX4/Survivin Axis in Rat Thy-1 Nephritis

Yao

Liu

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: The activation of complement system and the formation of C5b-9 complex have been confirmed in the glomeruli of patients with mesangioproliferative glomerulonephritis (MsPGN). However, the role and mechanism of C5b-9-induced injury in glomerular mesangial cell (GMC) are poorly understood. Rat Thy-1N is an animal model for studying MsPGN. It has been revealed that the attack of C5b-9 to the GMC in rat Thy-1N is sublytic, and sublytic C5b-9 can cause GMC apoptosis, but the underlying mechanism is not fully elucidated. To explore the role and regulatory mechanism of C5b-9 in MsPGN lesion, we used rat Thy-1N model and first detected the change of microRNA (miRNA) profiles both in Thy-1N rat renal tissues (in vivo) and in the cultured GMCs with sublytic C5b-9 stimulation (in vitro). Then we determined the effect of miR-3546, which increased both in vivo and in vitro, on GMC apoptosis upon sublytic C5b-9 as well as the involved mechanism. Methods: Rat Thy-1N model was established and GMCs were treated with sublytic C5b-9. The rat renal cortex and the stimulated GMCs were obtained for miRNA microarray detection. Subsequently, the increased miRNAs were verified by real-time PCR. Meanwhile, to ascertain the ability of some miRNAs to upregulate cleaved caspase 3 and induce GMC apoptosis, the corresponding miRNA mimics were transfected into GMCs, followed by western blotting (WB) and flow cytometry mesurement. Thereafter, the miR-3546-targeted gene (SOX4) was predicted using bioinformatics approaches, and SOX4 expression in Thy-1N tissues and in the GMCs upon sublytic C5b-9 stimulation or miR-3546 mimic/inhibitor transfection were detected using real-time PCR and WB. To prove that miR-3546 can affect SOX4 gene transcription and SOX4 can regulate survivin expression, dual luciferase reporter assay, real-time PCR, WB and chromatin immunoprecipitation (ChIP) assays were performed. Furthermore, the role of miR-3546/SOX4/survivin axis in the GMC apoptosis induced by sublytic C5b-9 was examined using WB and flow cytometry. Results: Compared with normal renal tissues and untreated GMCs, there were 43 and 62 upregulated miRNAs (> 2-fold) in Thy-1N tissues and sublytic C5b-9-stimulated GMCs respectively. A total of 17 miRNAs were increased both in vivo and in vitro, 11 of which were validated by real-time PCR. Among them, miR-3546 could markedly promote GMC apoptosis and inhibit SOX4 or survivin expression in response to sublytic C5b-9, and either SOX4 or survivin overexpression markedly rescued the GMC apoptosis mediated by miR-3546 mimic. Additionally, SOX4 overexpression could reverse the survivin suppression by miR-3546 mimic, and SOX4 could bind to survivin promoter (-1,278 to -853 nt) and activate survivin gene transcription. Conclusion: MiR-3546/ SOX4/survivin axis has a promoting role in the GMC apoptosis triggered by sublytic C5b-9, and our findings may provide a new insight into the pathogenesis of rat Thy-1N and human MsPGN.

show abstract

MicroRNA deep sequencing reveals chamber-specific miR-208 family expression patterns in the human heart

Cited by 43 publications

References 41 publications

microRNAs in cardiovascular disease – clinical application

microRNAs in cardiovascular disease – clinical application

Distribution of microRNA biomarker candidates in solid tissues and body fluids

Sublytic C5b-9 Induces Glomerular Mesangial Cell Apoptosis Through miR-3546/SOX4/Survivin Axis in Rat Thy-1 Nephritis

Contact Info

Product

Resources

About