miRNAs in Health and Disease

Abstract

microRNAs (miRNAs) are small, non-coding RNA molecules (~19–24 nucleotides) that post-transcriptionally regulate gene expression by inducing mRNA degradation or translational repression. Since the discovery of lin-4 in 1993, a milestone honored with the 2024 Nobel Prize, miRNAs have been estimated to regulate over 60% of human protein-coding genes. This review examines the canonical and non-canonical biogenesis pathways of miRNAs, emphasizing their role as homeostatic rheostats across major physiological systems, including embryogenesis, immunity, metabolism, neurobiology, and cardiovascular function. Dysregulation of these evolutionarily conserved regulatory networks contributes to the pathogenesis of human disorders, notably cancer, neurodegeneration, metabolic disorders, and autoimmune conditions. Given their stability in biofluids, circulating miRNAs have potential as diagnostic and prognostic biomarkers; however, most candidate signatures remain investigational and require prospective clinical validation. Therapeutic strategies based on miRNA mimics and inhibitors have reached preclinical and early-phase clinical testing, with outcomes ranging from completed proof-of-concept studies to terminated trials. Advances in nanotechnology, high-throughput sequencing, CRISPR-based tools, and precision medicine support the development of miRNA-based diagnostics and therapeutics, but routine clinical use still depends on standardized assays, reliable delivery, and evidence of safety and clinical benefit in the relevant biological context.