Uncovering potential differentially expressed miRNAs and targeted mRNAs in myocardial infarction based on integrating analysis

Wang, Shiai; Cao, Na

doi:10.3892/mmr.2020.11517

Cited by 9 publications

(6 citation statements)

References 89 publications

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“…In the present study, the JASPAR database was used to predict the binding sites between PDE4B promoter and JDP2, a transcription factor that is differentially expressed in patients with MI (38). In view of the critical regulatory role of JDP2 in impaired cardiac function (17), the present study also confirmed that JDP2 was upregulated in H9c2 cells exposed to H/R, and verified the interaction between JDP2 and the PDE4B promoter region.…”

Section: Discussionsupporting

confidence: 70%

Transcription factor JDP2 activates PDE4B to participate in hypoxia/reoxygenation‑induced H9c2 cell injury

Chen

Jia

et al. 2022

Exp Ther Med

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Myocardial ischemia/reperfusion (I/R) injury is a clinical challenge in the treatment of acute myocardial infarction (AMI). Phosphodiesterase 4B (PDE4B) expression is upregulated in AMI tissues. Thus, the present study aimed to investigate the role of PDE4B in myocardial I/R injury. H9c2 cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) to establish an in vitro myocardial I/R model. PDE4B expression was detected via reverse transcription-quantitative PCR (RT-qPCR) and western blotting before and after transfection with PDE4B interference plasmids in H/R-stimulated H9c2 cells. Cell viability and cytotoxicity were assessed using the Cell Counting Kit-8 and lactate dehydrogenase assays, respectively. Furthermore, oxidative stress was assessed using malondialdehyde, superoxide dismutase and glutathione/glutathione oxidized ratio detection kits. Cell apoptosis was detected via a TUNEL assay and western blotting. c-Jun dimerization protein 2 (JDP2) expression was also detected via RT-qPCR and western blotting. The dual luciferase reporter and chromatin immunoprecipitation assays were performed to verify the interaction between JDP2 and PDE4B. Following co-transfection with PDE4B interference plasmid and JDP2 overexpression plasmid, cell viability, cytotoxicity, oxidative stress and cell apoptosis were assessed. The results demonstrated that PDE4B knockdown reversed H/R-induced loss of viability and cytotoxicity of H9c2 cells. H/R-induced oxidative stress and cardiomyocyte apoptosis were also alleviated by PDE4B knockdown. In addition, the transcription factor JDP2 was expressed at high levels in H/R-stimulated H9c2 cells, and JDP2 overexpression upregulated PDE4B expression. Notably, JDP2 overexpression partly reversed the ameliorative effect of PDE4B knockdown on H/R-induced H9c2 injury. Taken together, the results of the present study suggested that JDP2-activated PDE4B contributed to H/R-induced H9c2 cell injury.

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Section: Discussionsupporting

confidence: 70%

Transcription factor JDP2 activates PDE4B to participate in hypoxia/reoxygenation‑induced H9c2 cell injury

Chen

Jia

et al. 2022

Exp Ther Med

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“…To identify the DEcircRNAs-DEmiRNAs-DEmRNAs regulatory relationships, we performed the prediction of circRNA–miRNA and miRNA–mRNA interactions based on the popular online tools, and then constructed a ceRNA network following the “ceRNA network hypothesis”. In this ceRNA network, previous studies have confirmed that miR-3194-3p/AQP1 ( 43 ), miR-1246/AXIN2 ( 44 ), miR-326/E2F2 ( 45 ), miR-326/CDCA5 ( 46 ), and miR-17-3p/RGS2 ( 47 ), etc, interaction relations play important roles in the occurrence and development of various cancers. Notably, these researches also to some extent reflect the veracity of the predicted ceRNA network in the current study.…”

Section: Discussionsupporting

confidence: 55%

Identification of a dysregulated CircRNA-associated gene signature for predicting prognosis, immune landscape, and drug candidates in bladder cancer

Shen

Zhang

et al. 2022

Front. Oncol.

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Increasing evidences have demonstrated that circular RNA (circRNAs) plays a an essential regulatory role in initiation, progression and immunotherapy resistance of various cancers. However, circRNAs have rarely been studied in bladder cancer (BCa). The purpose of this research is to explore new circRNAs and their potential mechanisms in BCa. A novel ceRNA-regulated network, including 87 differentially expressed circRNAs (DE-circRNAs), 126 DE-miRNAs, and 217 DE-mRNAs was constructed to better understanding the biological processes using Cytoscape 3.7.1 based on our previously high-throughput circRNA sequencing and five GEO datasets. Subsequently, five randomly selected circRNAs (upregulated circ_0001681; downregulated circ_0000643, circ_0001798, circ_0006117 and circ_0067900) in 20 pairs of BCa and paracancerous tissues were confirmed using qRT-PCR. Functional analysis results determined that 772 GO functions and 32 KEGG pathways were enriched in the ceRNA network. Ten genes (PFKFB4, EDNRA, GSN, GAS1, PAPPA, DTL, TGFBI, PRSS8, RGS1 and TCF4) were selected for signature construction among the ceRNA network. The Human Protein Atlas (HPA) expression of these genes were consistent with the above sequencing data. Notably, the model was validated in multiple external datasets (GSE13507, GSE31684, GSE48075, IMvigor210 and GSE32894). The immune-infiltration was evaluated by 7 published algorithms (i.e., TIMER, CIBERSORT, CIBERSORT-ABS, QUANTISEQ, MCPCOUNTER, XCELL and EPIC). Next, Correlations between riskscore or risk groups and clinicopathological data, overall survival, recognized immunoregulatory cells or common chemotherapeutic agents of BCa patients were performed using wilcox rank test, chi-square test, cox regression and spearman’s correlation analysis; and, these results are significant. According to R package “GSVA” and “clusterProfiler”, the most significantly enriched HALLMARK and KEGG pathway was separately the ‘Epithelial Mesenchymal Transition’ and ‘Ecm Receptor Interaction’ in the high- vs. low-risk group. Additionally, the functional experiments in vitro also revealed that the overexpression of has_circ_0067900 significantly impaired the proliferation, migration, and invasion capacities of BCa cells. Collectively, the results of the current study provide a novel landscape of circRNA-associated ceRNA-regulated network in BCa. The ceRNA-associated gene model which was constructed presented a high predictive performance for the prognosis, immunotherapeutic responsiveness, and chemotherapeutic sensitivity of BCa. And, has_circ_0067900 was originally proposed as tumor suppressor for patients with BCa.

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“…[39] hsa-miR-27a-3p and hsa-miR-335-5p were crucial in IS, whereas hsa-miR-34a-5p was crucial in MI. [40,41] The above information may reveal some unique mechanisms underlying the diseases, suggest new disease markers, and provide a possible basis for predicting IS and MI, as well as identify potential therapeutic targets. The prediction of drugs may have a role in disease prevention.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics strategies to identify differences in molecular biomarkers for ischemic stroke and myocardial infarction

Wang,

Gao,

Chen

et al. 2023

Medicine

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Ischemic strokes (ISs) are commonly treated by intravenous thrombolysis using a recombinant tissue plasminogen activator; however, successful treatment can only occur within 3 hours after the stroke. Therefore, it is crucial to determine the causes and underlying molecular mechanisms, identify molecular biomarkers for early diagnosis, and develop precise preventive treatments for strokes. We aimed to clarify the differences in gene expression, molecular mechanisms, and drug prediction approaches between IS and myocardial infarction (MI) using comprehensive bioinformatics analysis. The pathogenesis of these diseases was explored to provide directions for future clinical research. The IS (GSE58294 and GSE16561) and MI (GSE60993 and GSE141512) datasets were downloaded from the Gene Expression Omnibus database. IS and MI transcriptome data were analyzed using bioinformatics methods, and the differentially expressed genes (DEGs) were screened. A protein–protein interaction network was constructed using the STRING database and visualized using Cytoscape, and the candidate genes with high confidence scores were identified using Degree, MCC, EPC, and DMNC in the cytoHubba plug-in. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were performed using the database annotation, visualization, and integrated discovery database. Network Analyst 3.0 was used to construct transcription factor (TF) – gene and microRNA (miRNA) – gene regulatory networks of the identified candidate genes. The DrugBank 5.0 database was used to identify gene–drug interactions. After bioinformatics analysis of IS and MI microarray data, 115 and 44 DEGS were obtained in IS and MI, respectively. Moreover, 8 hub genes, 2 miRNAs, and 3 TFs for IS and 8 hub genes, 13 miRNAs, and 2 TFs for MI were screened. The molecular pathology between IS and MI presented differences in terms of GO and KEGG enrichment pathways, TFs, miRNAs, and drugs. These findings provide possible directions for the diagnosis of IS and MI in the future.

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Uncovering potential differentially expressed miRNAs and targeted mRNAs in myocardial infarction based on integrating analysis

Cited by 9 publications

References 89 publications

Transcription factor JDP2 activates PDE4B to participate in hypoxia/reoxygenation‑induced H9c2 cell injury

Transcription factor JDP2 activates PDE4B to participate in hypoxia/reoxygenation‑induced H9c2 cell injury

Identification of a dysregulated CircRNA-associated gene signature for predicting prognosis, immune landscape, and drug candidates in bladder cancer

Bioinformatics strategies to identify differences in molecular biomarkers for ischemic stroke and myocardial infarction

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