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Published on: February 3, 2023
Transcriptome sequencing and lncRNA-miRNA-mRNA network construction in cardiac fibrosis and heart failure
Shuo Wang1, Tianjie Lv1, Qincong Chen1
1Department of Cardiovasology, Shijiazhuang People's Hospital, Shijiazhaung, HB, China.
Insights
Researchers identified shared molecular markers between cardiac fibrosis (CF) and heart failure (HF). These common biomarkers, including specific mRNAs, lncRNAs, and miRNAs, could aid in early diagnosis and treatment to prevent CF progression to HF.
Area of Science:
- Molecular biology
- Genomics
- Cardiovascular research
Background:
- Cardiac fibrosis (CF) and heart failure (HF) are significant cardiovascular diseases.
- Severe CF can progress to HF, highlighting the need for early diagnostic and therapeutic strategies.
- Identifying common molecular underpinnings is crucial for understanding disease progression and developing targeted interventions.
Purpose of the Study:
- To identify common molecular markers (mRNAs, lncRNAs, miRNAs) between cardiac fibrosis and heart failure.
- To explore the diagnostic and therapeutic potential of these shared biomarkers.
- To construct a gene interaction network to pinpoint key molecules involved in both conditions.
Main Methods:
- High-throughput sequencing for RNA library construction.
- Differential expression analysis using DESeq2 to identify DEmRNAs, DElncRNAs, and DEmiRNAs.
- ConsensusPathDB for functional enrichment analysis and gene interaction network construction.
- RT-PCR for verification and analysis of public datasets (GSE104150, GSE21125) for validation.
Main Results:
- Identified 146 shared DEmRNAs, 80 shared DElncRNAs, and 6 shared DEmiRNAs between CF and HF.
- Constructed a lncRNA-miRNA-mRNA network, highlighting key molecules like hsa-miR-144-3p and CCNE2.
- Hsa-miR-144-3p and CCNE2 showed potential as diagnostic biomarkers for HF.
Conclusions:
- The study identified common molecular biomarkers for cardiac fibrosis and heart failure.
- These shared markers may facilitate early detection and intervention, potentially preventing the transition from CF to HF.
- Hsa-miR-144-3p and CCNE2 represent promising candidates for future diagnostic and therapeutic development in cardiovascular diseases.
Abstract:
Cardiac fibrosis (CF) and heart failure (HF) are common heart diseases, and severe CF can lead to HF. In this study, we tried to find their common potential molecular markers, which may help the diagnosis and treatment of CF and HF. RNA library construction and high-throughput sequencing were performed. The DESeq2 package in R was used to screen differentially expressed mRNAs (DEmRNAs), differentially expressed lncRNA (DElncRNAs) and differentially expressed miRNA (DEmiRNAs) between different samples. The common DEmRNAs, DElncRNAs and DEmiRNAs for the two diseases were obtained. The ConsensusPathDB (CPDB) was used to perform biological function enrichment for common DEmRNAs. Gene interaction network was constructed to screen out key genes. Subsequently, real-time polymerase chain reaction (RT-PCR) verification was performed. Lastly, GSE104150 and GSE21125 data sets were utilized for expression validation and diagnostic analysis. There were 1477 DEmRNAs, 502 DElncRNAs and 36 DEmiRNAs between CF and healthy control group. There were 607 DEmRNAs, 379DElncRNAs,s and 42 DEmiRNAs between HF and healthy control group. CH and FH shared 146 DEmRNAs, 80 DElncRNAs, and 6 DEmiRNAs. Hsa-miR-144-3p, CCNE2, C9orf72, MAP3K20-AS1, LEF1-AS1, AC243772.2, FLJ46284, and AC239798.2 were key molecules in lncRNA-miRNA-mRNA network. In addition, hsa-miR-144-3p and CCNE2 may be considered as potential diagnostic gene biomarkers in HF. In this study, the identification of common biomarkers of CF and HF may help prevent CF to HF transition as early as possible.

