Dataset Information

Differentially expressed lncRNAs, miRNAs and mRNAs with associated ceRNA networks in a mouse model of myocardial ischemia/reperfusion injury.

ABSTRACT: Non?coding RNAs, including long non?coding RNAs (lncRNAs) and microRNAs (miRNAs/miRs), have significant regulatory effects on a number of biological processes in myocardial ischemia/reperfusion (I/R) injury, including cell differentiation, proliferation and apoptosis. In the present study, the expression levels of lncRNAs, miRNAs and mRNAs were evaluated in a mouse model of myocardial I/R injury. The potential functions of these differentially expressed genes were then analyzed via Gene Ontology and pathway analyses. Additionally, the interactions between lncRNA?miRNA?mRNA were predicted by constructing a competing endogenous RNA regulatory network. It was found that 14,366 lncRNAs, 151 miRNAs and 9,377 mRNAs were differentially expressed in mice hearts after I/R compared with the Sham group (fold change >2; P<0.05). The results indicated that these differentially expressed genes were involved in multiple molecular functions, including 'guanosine diphosphate binding', 'RNA polymerase II carboxy?terminal domain kinase activity', 'TATA?binding protein?class protein binding', 'nicotinamide adenine dinucleotide binding' and 'protein phosphatase type 2A regulator activity'. The interactions between lncRNA?miRNA?mRNA, including five lncRNAs, 38 miRNAs and 196 mRNAs, were predicted, specifically Gm12040?mmu?miR?125a?5p?decapping mRNA 1B, Rpl7l1?ps1?mmu?miR?124?3p?G protein?coupled receptor 146, Gm11407?mmu?miR?190a?5p?homeobox and leucine zipper encoding (HOMEZ), 1600029O15Rik?mmu?miR?132?3p?HOMEZ and AK155692?mmu?miR?1224?3p?activating transcription factor 6?. Collectively, these findings provided novel insights for future research on lncRNAs, miRNAs and mRNAs in myocardial I/R injury.

SUBMITTER: Zhang R

PROVIDER: S-EPMC7411395 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Differentially expressed lncRNAs, miRNAs and mRNAs with associated ceRNA networks in a mouse model of myocardial ischemia/reperfusion injury.

Zhang Rui R Wang Jiali J Liu Baoshan B Wang Wenjun W Fan Xinhui X Zheng Boyuan B Yuan Qiuhuan Q Xue Mengyang M Xu Feng F Guo Ping P Chen Yuguo Y

Molecular medicine reports 20200706 3

Non‑coding RNAs, including long non‑coding RNAs (lncRNAs) and microRNAs (miRNAs/miRs), have significant regulatory effects on a number of biological processes in myocardial ischemia/reperfusion (I/R) injury, including cell differentiation, proliferation and apoptosis. In the present study, the expression levels of lncRNAs, miRNAs and mRNAs were evaluated in a mouse model of myocardial I/R injury. The potential functions of these differentially expressed genes were then analyzed via Gene Ontology ...[more]

PMID: 32705277

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Project description:BackgroundAdult degenerative scoliosis (ADS) is forecast to be a prevalent disabling condition in an aging society. Universally, its pathogenesis is perceived as intervertebral disc degeneration (IDD), however, a thought-provoking issue is why precisely a subset of patients with disc degeneration develop ADS. Exploring the diversities between common IDD and ADS would contribute to unraveling the etiological mechanisms of ADS. Therefore, we aimed to integrate the circRNA, lncRNA, miRNA, and mRNA expression profiles from normal adults (Normal), patients with lumbar disc herniation (LDH), and ADS by whole transcriptome sequencing, which identifies critical functional ncRNA and ceRNA networks and crosstalk between the various transcripts.MethodsThe fresh whole blood samples (n = 3/group) were collected from ADS patients, LDH patients, and healthy volunteers (Normal group), which were examined for mRNA, miRNA, lncRNA, and circRNA expression and screened for differentially expressed (DE) ncRNAs. Then, Gene Ontology (GO) and KEGG analyses were performed for gene annotation and enrichment pathways on the DE RNAs, which were constructed as a lncRNA-miRNA-mRNA network. Eventually, DE RNAs were validated by qRT-PCR targeting disc nucleus pulposus (NP) tissue in ADS and LDH group (n = 10/group).ResultsCompared to the LDH group, we identified 3322 DE mRNAs, 221 DE lncRNAs, 20 DE miRNAs, and 15 DE circRNAs in the ADS. In contrast to Normal, 21 miRNAs and 19 circRNAs were differentially expressed in the ADS. The expression of multiple differentially expressed ncRNAs was confirmed by qRT-PCR analysis to be consistent with the sequencing results. In addition, GO, and KEGG analysis demonstrated that most DE mRNAs and ncRNAs target genes are involved in various biological processes, including Endocytosis, Apoptosis, Rap1 signaling pathway, Notch signaling pathway, and others. The constructed lncRNA-miRNA-mRNA co-expression network was primarily related to angiogenesis and regulation.ConclusionBy focusing on comparing asymmetric and symmetric disc degeneration, whole-transcriptome sequencing and bioinformatics analysis systematically screened for key ncRNAs in the development of ADS, which provided an abundance of valuable candidates for the elucidation of regulatory mechanisms. The DE ncRNAs and the lncRNA-miRNA-mRNA network are intrinsically involved in the regulation of mediator and angiogenesis, which may contribute to the insight into the pathogenesis of ADS.

Project description:Competitive endogenous RNA regulation suggests an intricate network of all transcriptional RNAs that have the function of repressing miRNA function and regulating mRNA expression. Today, the specific ceRNA regulatory mechanisms of lncRNA-miRNA-mRNA in patients who have diabetes mellitus (DM) and myocardial infarction (MI) are still unknown. Two data sets, GSE34198 and GSE112690, were rooted in the Gene Expression Omnibus database to search for changes of lncRNA, miRNA, and mRNA in MI patients with diabetes. Weighted gene correlation network analysis (WGCNA) was used to identify the modules related to the development of diabetes in patients with MI. Target genes of miRNAs were predicted using miRWalk, TargetScan, mirDB, RNA22, and miRanda. Then, functional and enrichment analyses were performed to build the lncRNA-miRNA-mRNA interaction network. We built ceRNA regulatory networks with three lncRNAs, two miRNAs, and nine mRNAs. Differentially expressed genes enriched in biological process, including neutrophil activation, refer to immune response and positive system of defense feedback. Besides, there is significant enrichment in molecular function of calcium toll-like receptor binding, icosanoid binding, RAGE receptor binding, and arachidonic acid binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis enriched differentially expressed genes (DEGs) in pathways that were well known in MI, indicating inflammation and immune response. Pathways associated with diabetes were also significantly enriched. We confirmed significantly altered lncRNA, miRNA, and mRNA in MI patients with diabetes, which might serve as biomarkers for the progress and development of diabetic cardiovascular diseases. We constructed a ceRNA regulatory network of lncRNA-miRNA-mRNA, which will enable us to understand the novel molecular mechanisms included in the initiation, progression, and interaction between DM and MI, laying the foundation for clinical diagnosis and treatment.

Dataset Information

Differentially expressed lncRNAs, miRNAs and mRNAs with associated ceRNA networks in a mouse model of myocardial ischemia/reperfusion injury.

Publications

Differentially expressed lncRNAs, miRNAs and mRNAs with associated ceRNA networks in a mouse model of myocardial ischemia/reperfusion injury.

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