Uncovering a Conserved miRNA Hallmark Across Diverse SARS-CoV-2-Infected Cellular Models
MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression and play a fundamental role in host response to viral infections. SARS-CoV-2 has been shown to dysregulate host miRNA expression, potentially as a mechanism to modulate cellular pathways for its own replication or to evade immune responses. However, evidence from the literature related to the specific miRNA landscape in SARS-CoV-2 infection is conflicting and unclear. We employed an integrative multi-model approach using human nasal lung epithelial cell lines and pulmonary organoids to map miRNA expression dynamics after SARS-CoV-2 infection. Data obtained from the CALU-3 miRNAome were successively validated in other two cellular models (hAEC and hLORG), and from this comparative analysis, two miRNAs, miR-141-3p and miR-33a-5p, were found to be significantly dysregulated. These miRNAs are involved in critical pathways, including cytokine-mediated signalling, apoptotic processes and epithelial cell junction integrity. High-throughput miRNA profiling was followed by functional enrichment analysis of their predicted targets to delineate affected biological pathways. By highlighting candidate miRNAs and regulatory pathways that may contribute to disease pathogenesis, we identified robust, infection-associated hallmarks across cell models, establishing a foundation for future therapeutic strategies for COVID-19 based on the development of miRNA-guided approaches.