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pmid:37562973
miRNA-103-3p-Hlf regulates apoptosis and autophagy by targeting hepatic leukaemia factor in heart failure.
Pengcheng Xue · Yang Liu · Haifeng Wang · Junling Huang · Ming Luo
ESC heart failure · 2023 doi:10.1002/ehf2.14493
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Experiment
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Complete file
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This study aims to investigate the underlying mechanisms of HF in terms of expression and regulation patterns using bioinformatics and experimental validation.\nMETHODS AND RESULTS: Two HF datasets were collected: a dataset GSE112056 downloaded from the GEO database (including mRNA and miRNA sequencing data) and another is the laboratory-owned mRNA dataset. Differential mRNAs and miRNAs in the two datasets were screened using the raw Bayesian approach method. Gene Ontology was used to perform functional enrichment analysis of the differential mRNAs and co-expression network analysis of the differential mRNAs, combined with nuclear transcription factors in the differential miRNAs and mRNAs for target gene prediction. A HF cell model was constructed using mouse cardiomyocytes (HL-1), and the role and mechanism of miRNA-103-3p-Hlf (hepatic leukaemia factor) in the process of HF was verified by cell transfection, luciferase reporter gene, WB, and qPCR. We found that Hlf gene expression was decreased in the HF model group and strongly correlated with FYCO1 (FYVE and coiled-coil domain-containing protein 1) gene, a phenomenon enriched in apoptotic autophagy-related pathways. MiR-103-3p expression was up-regulated in the HF model group, and its targeting correlation with Hlf was confirmed by luciferase activity assay. In the HL-1 cell model, miR-103-3p significantly promoted apoptosis and inhibited autophagy in HL-1 cells (all P < 0.05), and overexpression of the Hlf gene reversed this phenomenon, inhibiting apoptosis and promoting autophagy in HL-1 cells (all P < 0.05).\nCONCLUSIONS: MiR-103-3p affects myocardial cells apoptosis and autophagy by targeting Hlf, playing as a potential therapeutic biomarker for HF progression.", "claims": [{"id": "claim-method", "statement": "DEGs between HF model (TAC) groups and sham operation groups were respectively analysed using the limma package in R, including background correction and expression value normalization.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37562973", "locator": "sections[3] \"Identifcation of differentially expressed genes in heart failure and functional enrichment analysis\" paragraph 2", "quote": "DEGs between HF model (TAC) groups and sham operation groups were respectively analysed using the limma package in R, including background correction and expression value normalization."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Two HF datasets were collected: a dataset GSE112056 downloaded from the GEO database (including mRNA and miRNA sequencing data) and another is the laboratory‐owned mRNA dataset.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37562973", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Two HF datasets were collected: a dataset GSE112056 downloaded from the GEO database (including mRNA and miRNA sequencing data) and another is the laboratory‐owned mRNA dataset."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The limma analysis identified 132 differentially expressed genes, consisting of 83 up-regulated and 49 down-regulated genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37562973", "locator": "sections[15] \"Identification of microRNA‐103‐3p targeting Hlf/Fyco1 by bioinformatics analysis\" paragraph 2", "quote": "Based on the limma analysis, a total of 132 DEGs were identified, consisting of 83 genes that were up‐regulated and 49 genes that were down‐regulated, which suggested that DEGs could distinguish between patients with TAC groups and sham operation groups."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The limma analysis identified 132 differentially expressed genes, consisting of 83 up-regulated and 49 down-regulated genes.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37562973"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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