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Novel lncRNA-miRNA-mRNA Competing Endogenous RNA Triple Networks Associated Programmed Cell Death in Heart Failure
Yu Zheng1, Yingjie Zhang1, Xiu Zhang1
1Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Insights
This study reveals novel competing endogenous RNA (ceRNA) networks involving long non-coding RNA GAS5 in heart failure (HF). These networks regulate programmed cell death, offering new insights into HF pathophysiology.
Area of Science:
- Molecular Biology
- Genetics
- Cardiovascular Diseases
Background:
- Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) form regulatory networks crucial in cardiovascular diseases.
- The specific role of lncRNA-mediated competing endogenous RNA (ceRNA) networks in heart failure (HF) pathogenesis remains largely unexplored.
Purpose of the Study:
- To investigate the function of lncRNA-mediated ceRNA networks in the pathophysiological processes of HF.
- To explore the regulatory roles of these networks in programmed cell death during HF development.
Main Methods:
- Bioinformatic analysis of public datasets (GSE77399, GSE52601, GSE57338) to identify differentially expressed lncRNAs, miRNAs, and mRNAs.
- Construction of lncRNA-miRNA-mRNA ceRNA networks and enrichment analysis (GO, KEGG) to predict biological functions.
- Validation of identified ceRNA regulatory pathways related to programmed cell death using qRT-PCR.
Main Results:
- Two lncRNA-mediated ceRNA networks, comprising two lncRNAs, eight miRNAs, and 65 mRNAs, were constructed for HF.
- Enrichment analysis indicated involvement in extracellular matrix biological processes.
- Seven specific lncRNA GAS5-mediated ceRNA pathways impacting programmed cell death (apoptosis, ferroptosis, pyroptosis) were identified and validated.
Conclusions:
- Novel ceRNA regulatory networks involving lncRNA GAS5 in HF were discovered through bioinformatic analysis.
- These networks are hypothesized to play significant roles in programmed cell death pathways relevant to HF.
- The findings provide new perspectives and potential research directions for understanding ceRNA networks in HF.
Abstract:
Objective: Increasing evidence has uncovered the roles of lncRNA-miRNA-mRNA regulatory networks in cardiovascular diseases. However, the crosstalk between ceRNA networks and development of heart failure (HF) remains unclear. This study was to investigate the role of lncRNA-mediated ceRNA networks in the pathophysiological process of HF and its potential regulatory functions on programmed cell death. Methods: We firstly screened the GSE77399, GSE52601 and GSE57338 datasets in the NCBI GEO database for screening differentially expressed lncRNAs, miRNAs and mRNAs. lncRNA-miRNA-mRNA regulatory networks based on the ceRNA theory were subsequently constructed. GO and KEGG enrichment analysis was conducted to predict potential biological functions of mRNAs in ceRNA networks. Differentially expressed mRNAs were then interacted with programmed cell death related genes. lncRNA-mediated ceRNA regulatory pathways on programmed cell death were validated with qRT-PCR testing. Results: Based on our bioinformatic analysis, two lncRNAs, eight miRNAs and 65 mRNAs were extracted to construct two lncRNAs-mediated ceRNA networks in HF. Biological processes and pathways were enriched in extracellular matrix. Seven lncRNA-mediated ceRNA regulatory pathways on programmed cell death, GAS5/miR-345-5p/ADAMTS4, GAS5/miR-18b-5p/AQP3, GAS5/miR-18b-5p/SHISA3, GAS5/miR-18b-5p/C1orf105, GAS5/miR-18b-5p/PLIN2, GAS5/miR-185-5p/LPCAT3, and GAS5/miR-29b-3p/STAT3, were finally validated. Conclusions: Two novel ceRNA regulatory networks in HF were discovered based on our bioinformatic analysis. Based on the interaction and validation analysis, seven lncRNA GAS5-mediated ceRNA regulatory pathways were hypothesized to impact programmed cell death including seven for apoptosis, three for ferroptosis, and one for pyroptosis. Upon which, we provided novel insights and potential research plots for bridging ceRNA regulatory networks and programmed cell death in HF.
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