High level of circulating microRNA-142 is associated with acute myocardial infarction and reduced survival

Vastrad²,

et al. 2022

Preprint

Objectives The underlying molecular mechanisms of diabetic nephropathy (DN) have yet not been investigated clearly. In this investigation, we aimed to identify key genes involved in the pathogenesis and prognosis of DN. Methods We downloaded next generation sequencing (NGS) dataset GSE142025 from Gene Expression Omnibus (GEO) database having 28 DN samples and 9 normal control samples. The differentially expressed genes (DEGs) between DN and normal control samples were analyzed. Biological function analysis of the DEGs was enriched by GO and REACTOME pathway. Then we established the protein-protein interaction (PPI) network, modules, miRNA-DEG regulatory network and TF-DEG regulatory network. Hub genes were validated by using receiver operating characteristic (ROC) curve analysis. Results A total of 549 DEGs were detected including 275 up regulated and 274 down regulated genes. Biological process analysis of functional enrichment showed these DEGs were mainly enriched in cell activation, integral component of plasma membrane, lipid binding and biological oxidations. Analyzing the PPI network, miRNA-DEG regulatory network and TF-DEG regulatory network, we screened hub genes MDFI, LCK, BTK, IRF4, PRKCB, EGR1, JUN, FOS, ALB and NR4A1 by the Cytoscape software. The ROC curve analysis confirmed that hub genes were of diagnostic value. Conclusions Taken above, using integrated bioinformatics analysis, we have identified key genes and pathways in DN, which could improve our understanding of the cause and underlying molecular events, and these key genes and pathways might be therapeutic targets for DN.

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics analysis reveals novel key biomarkers in diabetic nephropathy

Vastrad²,

et al. 2022

Preprint

“…TNFSF14 [47], ITGAL (integrin subunit alpha L) [48], PLAC8 [49], ADRA2A [50], CCL21 [51], ALOX5 [52], CNR2 [53], COL1A1 [54], WNT7A [55], SLAMF1 [56], CD3D [57], LTF (lactotransferrin) [58], MIR27B [59], PDK4 [60], UCN3 [61], PCK1 [62], CEL (carboxyl ester lipase) [63], TRPM6 [64], MTTP (microsomal triglyceride transfer protein) [65], CYP2C8 [66] and CYP3A4 [67] have important role in the progression of type 2 diabetes via in ammation , but these genes might be crucial role in DN progression. Zhang et al [68], Ellenbroek et al [69], Guo et al [70] and Tillmanns et al [71] have shown that MZB1, LAIR1, MIR142 and FAP ( broblast activation protein alpha) modulating mitochondrial function and alleviating in ammation in myocardial infarction, but these genes might be involved in progression of DN. IRF4 plays a key role in the obesity-induced insulin resistance [72], but this gene might be responsible for development of DN.…”

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics analysis reveals novel key biomarkers and potential candidate small molecule drugs in diabetic nephropathy

Vastrad²,

et al. 2020

Preprint

The underlying molecular mechanisms of diabetic nephropathy (DN) have yet not been investigated clearly. In this investigation, we aimed to identify key genes involved in the pathogenesis and prognosis of DN. We selected expression profiling by high throughput sequencing dataset GSE142025 from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between DN and normal control samples were analyzed with limma package. Gene ontology (GO) and REACTOME enrichment analysis were performed using ToppGene. Then we established the protein-protein interaction (PPI) network, miRNA-DEG regulatory network and TF-DEG regulatory network. The diagnostic values of hub genes were performed through receiver operating characteristic (ROC) curve analysis. Finally, the candidate small molecules as potential drugs to treat DM were predicted using molecular docking studies. Through expression profiling by high throughput sequencing dataset, a total of 549 DEGs were detected including 275 up regulated and 274 down regulated genes. Biological process analysis of functional enrichment showed these DEGs were mainly enriched in cell activation, response to hormone, cell surface, integral component of plasma membrane, signaling receptor binding, lipid binding, immunoregulatory interactions between a lymphoid and a non-lymphoid cell and biological oxidations. DEGs with high degree of connectivity (MDFI, LCK, BTK, IRF4, PRKCB, EGR1, JUN, FOS, ALB and NR4A1) were selected as hub genes from protein-protein interaction (PPI) network, miRNA-DEG regulatory network and TF-DEG regulatory network. The ROC curve analysis confirmed that hub genes were high diagnostic values. Finally, the significant small molecules were obtained based on molecular docking studies. Our results indicated that MDFI, LCK, BTK, IRF4, PRKCB, EGR1, JUN, FOS, ALB and NR4A1 could be the potential novel biomarkers for GC diagnosis prognosis and the promising therapeutic targets. The present study may be crucial to understanding the molecular mechanism of DN initiation and progression.

“…Plasma levels of miRNAs have been used to monitor degenerative disease of the mitral valve (MV) but have not been widely adopted by the cardiology community [4,6,7,[9][10][11]. The lack of enthusiasm of cardiologists for investigations into degenerative aortic valve stenosis [6][7][8]12,13] can be partially deduced from the lack of positive findings in mitral valve degenerative diseases leading to regurgitation [14][15][16][17][18][19].…”

Section: The Importance Of Discovering Diagnostic Biomarkers For Mitral Valve Prolapsementioning

confidence: 99%

MicroRNAs in Valvular Heart Diseases: Biological Regulators, Prognostic Markers and Therapeutical Targets

Nappi

Iervolino

Singh

et al. 2021

IJMS

miRNAs have recently attracted investigators’ interest as regulators of valvular diseases pathogenesis, diagnostic biomarkers, and therapeutical targets. Evidence from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse development, aortic leaflet fusion, and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes of different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address miRNAs over or under-representation and thus, their impact on pathogeneses. In this review, we discuss the fundamental intra- and intercellular signals regulated by miRNAs leading to defects in mitral and aortic valves, congenital heart diseases, and the possible therapeutic strategies targeting them. These miRNAs inhibitors are comprised of antisense oligonucleotides and sponge vectors. The miRNA mimics, miRNA expression vectors, and small molecules are instead possible practical strategies to increase specific miRNA activity. Advantages and technical limitations of these new drugs, including instability and complex pharmacokinetics, are also presented. Novel delivery strategies, such as nanoparticles and liposomes, are described to improve knowledge on future personalized treatment directions.