Different Expressions of Pericardial Fluid MicroRNAs in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy and Ischemic Heart Disease Undergoing Ventricular Tachycardia Ablation

Khudiakov, Aleksandr; Panshin, D. D.; Fomicheva, Yulia; Knyazeva, Anastasia; Simonova, K. A.; Lebedev, Dmitry; Mikhaylov, Evgeny N.; Kostareva, Anna

doi:10.3389/fcvm.2021.647812

Cited by 13 publications

(8 citation statements)

References 68 publications

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“…In addition, another study suggested that miR-206 exhibits a profound effect on a series of myopathies, including hypertrophy, malnutrition, and conduction defects [41]. Besides, hsa-miR-206 is differentially expressed in patients with arrhythmic right ventricular cardiomyopathy [42]. Strikingly, a previous study highlighted that inhibition of miR-206 could improve mouse ischemia-reperfusion in arrhythmia models by targeting connexin 43 [43].…”

Section: Discussionmentioning

confidence: 99%

lncRNA ADAMTS9-AS1/circFN1 Competitively Binds to miR-206 to Elevate the Expression of ACTB, Thus Inducing Hypertrophic Cardiomyopathy

Feng

Han

2022

Oxidative Medicine and Cellular Longevity

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Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease and can result in substantial disability. The current study explored the potentials of long noncoding RNA- (lncRNA-) circular RNA- (circRNA-) microRNA- (miRNA-) messenger RNA (mRNA) networks in HCM. Firstly, HCM-related microarray data were procured from the GEO database, with differentially expressed genes (DEGs) obtained. HCM-related target genes were retrieved in combination with GeneCards and CTD databases, and candidate target genes were subsequently obtained by intersection screening. Further, an interaction network diagram of candidate target genes was constructed using the STRING database, and the hub genes in the network were determined according to the core degree. The “ClusterProfiler” package of the R software was adopted for GO and KEGG analyses of candidate target genes, to analyze the potential molecular pathways in HCM. Next, upstream miRNA, lncRNA, and circRNA of ACTB were predicted with RNAInter, mirDIP, TargetScan, DIANA-LncBase, and StarBase databases, followed by construction of lncRNA/circRNA-miRNA-mRNA coexpression networks. ACTB, miR-206, circFN1, and ADAMTS9-AS1 expression in peripheral blood samples from HCM patients and normal healthy controls were detected using RT-qPCR. Moreover, rat cardiomyocyte cell lines H9c2 and HEK293 cells were selected for in vitro verification of competitive endogenous RNA (ceRNA) regulation mechanism. A total of 15 candidate target genes related to HCM were screened using the online databases. Further protein-protein interaction analysis identified ACTB as the hub gene for HCM. The targeted binding relationship between miR-206, miR-145-5p, miR-1-3p, and ACTB was found. Furthermore, ADAMTS9-AS1 and circFN1 were discovered as the upstream genes of miR-206. Moreover, ADAMTS9-AS1, circFN1, and ACTB were found to be poorly expressed, and miR-206 was highly expressed in HCM. In vitro experimentation further confirmed that ADAMTS9-AS1 and circFN1 could competitively bind to miR-206, thereby augmenting ACTB expression. Taken all, ADAMTS9-AS1/circFN1-miR-206-ACTB regulatory network may involve in HCM occurrence, providing a novel theoretical basis for in-depth understanding of mechanism of HCM.

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Section: Discussionmentioning

confidence: 99%

lncRNA ADAMTS9-AS1/circFN1 Competitively Binds to miR-206 to Elevate the Expression of ACTB, Thus Inducing Hypertrophic Cardiomyopathy

Feng

Han

2022

Oxidative Medicine and Cellular Longevity

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“…In addition, hsa-let-7a-3p expression was downregulated in AF compared with SR [ 25 ]. Khudiakov et al showed that hsa-let-7a-3p was abnormally expressed in cardiovascular disease [ 26 ]. It is shown that let-7a-3p acts as a tumor suppressor and participates in the regulatory processes of proliferation and apoptosis in cancer cells [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of CeRNA Regulatory Networks in Atrial Fibrillation Using Nanodelivery

Lin¹,

Meng²,

Lyu³

2022

Evidence-Based Complementary and Alternative Medicine

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The initiation and maintenance of AF is a complex biological process that is the ultimate manifestation of many cardiovascular diseases. And the pathogenesis of atrial fibrillation (AF) is unclear. Therefore, this study aimed to find the potential competing endogenous RNAs (ceRNAs) network and molecular dysregulation mechanism associated with AF. GSE135445, GSE2240, and GSE68475 were obtained from the Gene Expression Omnibus (GEO). Differential analysis was utilized to identify the differentially expressed mRNAs, miRNAs, and lncRNAs between AF and sinus rhythms (SR). AF-associated mRNAs and nanomaterials were screened and their biological functions and KEGG signaling pathways were identified. Nanomaterials for targeted delivery are uniquely capable of localizing the delivery of therapeutics and diagnostics to diseased tissues. The target mRNAs and target lncRNAs of differentially expressed miRNAs were identified using TargetScan and LncBase databases. Finally, we constructed the ceRNAs network and its potential molecular regulatory mechanism. We obtained 643 AF-associated mRNAs. They were significantly involved in focal adhesion and the PI3K-Akt signaling pathway. Among the 16 differentially expressed miRNAs identified, 31 differentially expressed target mRNAs, as well as 5 differentially expressed target lncRNAs were identified. Among them, we obtained 2 ceRNAs networks (hsa-miR-125a-5p and hsa-let-7a-3p). The aberrant expression of network target genes in AF mainly activated the HIF-1 signaling pathway. We speculated that the interaction pairs of miR-125a-5p and let-7a-3p with target mRNAs and target lncRNAs may be involved in AF. Our findings have a positive influence on investigating the pathogenesis of AF and identifying potential therapeutic targets.

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“…Only a few studies have focused on the role of ncRNAs in ACM, and all have restricted their results to one species, namely miRNAs, concluding that they emerge as potentially useful biomarkers [ 51 , 52 , 53 , 54 , 55 , 56 , 57 , 59 , 61 , 92 , 93 ]. To the best of our knowledge, no studies have addressed the regulation of the Wnt/Hippo pathway by ncRNAs in the scenario of ACM.…”

Section: Non-coding Rnas In Acmmentioning

confidence: 99%

Non Coding RNAs as Regulators of Wnt/β-Catenin and Hippo Pathways in Arrhythmogenic Cardiomyopathy

et al. 2022

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Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy histologically characterized by the replacement of myocardium by fibrofatty infiltration, cardiomyocyte loss, and inflammation. ACM has been defined as a desmosomal disease because most of the mutations causing the disease are located in genes encoding desmosomal proteins. Interestingly, the instable structures of these intercellular junctions in this disease are closely related to a perturbed Wnt/β-catenin pathway. Imbalance in the Wnt/β-catenin signaling and also in the crosslinked Hippo pathway leads to the transcription of proadipogenic and profibrotic genes. Aiming to shed light on the mechanisms by which Wnt/β-catenin and Hippo pathways modulate the progression of the pathological ACM phenotype, the study of non-coding RNAs (ncRNAs) has emerged as a potential source of actionable targets. ncRNAs comprise a wide range of RNA species (short, large, linear, circular) which are able to finely tune gene expression and determine the final phenotype. Some share recognition sites, thus referred to as competing endogenous RNAs (ceRNAs), and ensure a coordinating action. Recent cancer research studies regarding the key role of ceRNAs in Wnt/β-catenin and Hippo pathways modulation pave the way to better understanding the molecular mechanisms underlying ACM.

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Different Expressions of Pericardial Fluid MicroRNAs in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy and Ischemic Heart Disease Undergoing Ventricular Tachycardia Ablation

Cited by 13 publications

References 68 publications

lncRNA ADAMTS9-AS1/circFN1 Competitively Binds to miR-206 to Elevate the Expression of ACTB, Thus Inducing Hypertrophic Cardiomyopathy

lncRNA ADAMTS9-AS1/circFN1 Competitively Binds to miR-206 to Elevate the Expression of ACTB, Thus Inducing Hypertrophic Cardiomyopathy

Identification of CeRNA Regulatory Networks in Atrial Fibrillation Using Nanodelivery

Non Coding RNAs as Regulators of Wnt/β-Catenin and Hippo Pathways in Arrhythmogenic Cardiomyopathy

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