Evaluating roles of miRNAs in cardiac fibrosis: a meta-analysis
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Cardiovascular diseases are the leading cause of mortality globally. Cardiac fibrosis is an essential component of changes that occur in heart’s size, shape, and composition, in response to cardiac disease or cardiac damage. Exosomes are extracellular vesicles that aid cell-cell communication and carry proteins, metabolites, nucleic acids, etc. miRNAs are small non-coding RNA molecules that can be transported by exosomes and are uniquely capable of facilitating long-term repair by altering the targeted cells’ transcriptome. Prior studies have demonstrated relationships between exosomal miRNA content and fibrosis in the heart. In this research, self-built scoring models and Partial Least Squares Regression (PLSR) modeling were used to find miRNAs that can downregulate cardiac fibrosis. miR-21, miR-33, miR-125b, miR-155-5p, miR-34a were identified as profibrotic miRNAs and miR-29b, miR-29a, miR-26a, miR-30c, miR-29c were identified as antifibrotic miRNAs. Few under-studied miRNAs were also identified that might be important regulators of cardiac fibrosis. Computational models were built to predict the extent of cardiac fibrosis with miRNAs’ fold-changes as inputs. A computational workflow was developed to predict the extent of cardiac fibrosis when exosomes with custom-designed packages of miRNA content will be injected into animal models. This analysis consolidates relationships between selected miRNAs and cardiac fibrosis, and can be used to inform experimental studies of cardiac remodeling.