Integrated Analysis of Hub Genes and miRNAs in Dilated Cardiomyopathy

Huang, Kai; Wen, Shuyan; Wang, Fangrui; Pang, Liewen; Wang, Yiqing; Sun, Xiaotian

doi:10.1155/2020/8925420

Cited by 17 publications

(18 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, Huang et al found that PIK3R1, which is up-regulated in DCM tissues, may be involved in the pathogenesis of DCM. 55 Therefore, the study of PIK3R1 in DCM may be an interesting and meaningful direction.…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of Dilated Cardiomyopathy-Related Genes via Bioinformatics Analysis

Wang¹,

Qiu²,

Yuan³

et al. 2022

IJGM

View full text Add to dashboard Cite

Purpose Dilated cardiomyopathy (DCM) is a type of cardiomyopathy that can easily cause heart failure and has a high mortality rate. Therefore, there is an urgent need to study the underlying mechanism of action of dilated cardiomyopathy. In the present study, we aimed to explore potential miRNA–mRNA pairs and drugs related to DCM. Methods The Microarray data were collected from the Gene Expression Omnibus (GEO) database. Bioinformatics analysis differentially expressed miRNAs and mRNAs in each microarray were obtained. The target genes of miRNAs were obtained from the miRWalk 2.0 database, and the intersection of these two gene sets (miRNA target genes and differentially expressed mRNAs in the microarray) was obtained. Pathway and Gene Ontology (GO) enrichment analyses were performed in the KOBAS database. Cytoscape software was used to construct the miRNA–mRNA network, and the final hub genes were obtained. Furthermore, we predicted several candidate drugs related to hub genes using DSigDB database. To confirm the abnormal expression of hub genes, qRT-PCR was performed. Results In total, eight differentially expressed miRNAs and 92 differentially expressed mRNAs were identified. In addition, 47 differentially expressed miRNA target genes were identified. According to the analysis results of the miRNA-mRNA network, we identified hsa-miR-551b-3p, hsa-miR-770-5p, hsa-miR-363-3p, PIK3R1, DDIT4 , and CXCR4 as hub genes in DCM. Several candidate drugs, which are related to the hug genes, were identified. Conclusion In conclusion, in our study, we identified several hub genes that may be involved in the pathogenesis of DCM. Several drugs related to these hub genes may be used as clinical therapeutic candidates.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification and Validation of Dilated Cardiomyopathy-Related Genes via Bioinformatics Analysis

Wang¹,

Qiu²,

Yuan³

et al. 2022

IJGM

View full text Add to dashboard Cite

show abstract

“…miR-144-3p, having the highest statistical signi cance in EVs, is crucial for cardiac function as its loss worsened heart failure phenotype resulting with impaired late remodeling and decreased LVEF 44 . Moreover, mir-144 was identi ed as an important regulatory node in DCM 45 and its expression was down-regulated both in samples from DCM patients and in a doxorubicin-induced rodent model of cardiomyopathy 46 . Another study supporting important role of mir-144 shows that its loss resulted in ventricular dilation and impaired contractility, whereas intravenous delivery of this miRNA reduced infarcted area and improved cardiac function including LV fractional shortening, end-systolic volume, end-diastolic volume and ejection fraction 47 .…”

Section: Discussionmentioning

confidence: 99%

MicroRNA Composition of Plasma Extracellular Vesicles: A Harbinger of Late Cardiotoxicity of Doxorubicin

Totoń‐Żurańska

Sulicka-Grodzicka

Seweryn

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: The use of doxorubicin is associated with an increased risk of acute and long-term cardiomyopathy. Despite the constantly growing number of cancer survivors, little is known about the transcriptional mechanisms which progress in the time leading to a severe cardiac outcome. It is also unclear whether long-term transcriptomic alterations related to doxorubicin use are similar to transcriptomic patterns present in patients suffering from other cardiomyopathies. Methods: We have sequenced miRNA from total plasma and extracellular vesicles (EVs) from 66 acute lymphoblastic leukemia (ALL) survivors and 61 healthy controls (254 samples in total). We analyzed processes regulated by differentially expressed circulating miRNAs and cross-validated results with the data of patients with clinically manifested cardiomyopathies. Results: We found that especially miRNAs contained within EVs may be particularly informative in terms of cardiomyopathy development and may regulate pathways related to neurotrophin, transforming growth factor beta or epidermal growth factor receptors (ErbB). We identified vesicular miR-144-3p and miR-423-3p as the most variable between groups and significantly correlated with echocardiographic parameters and for plasma: let-7g-5p, miR-16-2-3p. Vesicular miR-144-3p correlates with the highest number of echocardiographic parameters and is differentially expressed in the circulation of patients with dilated cardiomyopathy. We also found that distribution of particular miRNAs between of plasma and EVs (proportion between compartments) e.g., miR-184 in ALL is altered suggesting alterations in secretory and miRNA sorting mechanisms.Conclusions: Our results show that transcriptomic alterations which lead to cardiomyopathy development many years after doxorubicin treatment are reflected in circulating miRNA levels. Among miRNAs related to cardiac function we found vesicular miR-144-3p and miR-423-3p and let-7g-5p, miR-16-2-3p contained in total plasma. Selection of source for such studies (plasma or EVs) is of critical importance as distribution of some miRNA between plasma and EVs is altered in ALL survivors in comparison to healthy people which suggests that doxorubicin-induced changes include miRNA sorting and export to extracellular space.

show abstract

“…For instance, miR-770 was constructed as the core in ceRNA network, while the upstream circRNAs, including 6:37353557|37364143, and lncRNAs, such as MSTRG.137663.1, MSTRG.77826.15, MSTRG.131343.148, MSTRG.80502.2, and Gm10734-201, acted as sponge to regulate Zfp831, Map3k6, Fosb, Pik3r5, Rhoh, et al Previous studies shown miR-770 is the potential candidates for investigating the aging process by control Wnt/chemokines and cytokines-related in ammation signaling pathways [40]. And miR-770 was also believed to play critical roles in the development and pathological mechanisms of dilated cardiomyopathy [41]. In our ceRNA network, Zfp831 and Rhoh, the downstream target of miR-770, have been identi ed to play critical roles in the differentiation of T follicular helper cells and T cells [42,43].…”

Section: Discussionmentioning

confidence: 99%

Whole-Transcriptome Sequencing Analysis Reveal Mechanisms of Yiqi Huoxue Yangyin (YHY) Decoction in Ameliorating D-gal-induced Cardiac Aging

Wang

Xiu

Yang

et al. 2022

Preprint

View full text Add to dashboard Cite

Background Aging is a major factor for cardiovascular disease, and cardiac aging is closely related to the incidence of cardiovascular disease. Clarifying the mechanism of cardiac aging and finding reliable intervention is critical for preventing cardiovascular diseases and achieving healthy longevity. Traditional Chinese medicine Yiqi Huoxue Yangyin (YHY) decoction has unique advantages in the treatment of cardiovascular disease and aging. However, the associated molecular mechanisms remain unknown. Purpose The present study aimed to verify the efficacy of YHY decoction against cardiac aging in D-gal-induced mouse model, and explore the potential mechanisms of YHY decoction treatment through whole-transcriptome sequencing technique, providing novel insights into the molecular basis of YHY decoction in treating cardiac aging. Methods The component of YHY decoction was identified by High Performance Liquid Chromatography (HPLC). D-gal-induced aging mouse model was established for this study. HE and Masson staining were applied to determined pathological changes of heart; telomere length, telomerase activity, AGEs and p53 were used to evaluated the degree of heart aging. Transcriptome sequencing, GO, KEGG, GSEA and ceRNA network were applied to analyzing the potential mechanisms of YHY decoction treatment of cardiac aging. Results In this study, we found that YHY decoction not only improved the pathological structure of aging heart, but also regulated the expression of aging-related markers, telomere length, telomerase activity, AGEs and p53, in the myocardial tissue, suggesting that it has a specific effect in delaying cardiac aging. Whole-transcriptome sequencing showed that the total of 433 mRNAs, 284 lncRNAs, 62 miRNAs, and 39 circRNAs were significantly differentially expressed after YHY decoction treatment. According to the analysis results of KEGG and GSEA, the differentially expressed mRNAs were found significantly involved in immune system, cytokine-cytokine receptor interaction and cell adhesion molecules. The ceRNA network showed that miR-770, miR-324, and miR-365 are localized in the center, mainly affecting the immune system, PI3K-Akt signaling pathway, and MAPK signaling pathway. Conclusion In conclusion, our results evaluated the ceRNA network of YHY decoction in treating cardiac aging for the first time, which could provide a better understanding of the potential mechanisms of YHY decoction treatment of cardiac aging.

show abstract

Integrated Analysis of Hub Genes and miRNAs in Dilated Cardiomyopathy

Cited by 17 publications

References 41 publications

Identification and Validation of Dilated Cardiomyopathy-Related Genes via Bioinformatics Analysis

Identification and Validation of Dilated Cardiomyopathy-Related Genes via Bioinformatics Analysis

MicroRNA Composition of Plasma Extracellular Vesicles: A Harbinger of Late Cardiotoxicity of Doxorubicin

Whole-Transcriptome Sequencing Analysis Reveal Mechanisms of Yiqi Huoxue Yangyin (YHY) Decoction in Ameliorating D-gal-induced Cardiac Aging

Contact Info

Product

Resources

About