Cigarette Smoking-Induced MicroRNA Dysregulation: From Molecular Mechanisms to Systemic Disease Networks and Therapeutic Implications

Background: MicroRNAs (miRNAs) are small non‑coding transcripts that regulate gene expression and modulate diverse cellular processes, including proliferation, apoptosis, and immune responses. Cigarette smoking (CS) remains the leading preventable cause of global morbidity and mortality, with tobacco smoke comprising over 7,000 chemicals that inflict cellular damage through oxidative stress, DNA adduction, and epigenetic reprogramming. Accumulating evidence has established miRNAs as critical mediators of CS‑induced pathogenesis, with miRNA dysregulation now recognized as a fundamental mechanism linking smoking to a wide spectrum of human diseases. This review synthesizes current knowledge on the roles of miRNAs in smoking‑related malignancies, chronic respiratory diseases, cardiovascular disorders, psychiatric illnesses, dermatological conditions, and gastrointestinal diseases. Materials and Methods: This narrative review searched PubMed, Web of Science, Scopus, and ScienceDirect (2007–2025). Seventy-three eligible studies on miRNA dysregulation in smoking-related diseases were qualitatively synthesized to assess molecular mechanisms and clinical potential. Results: The Rotterdam Study identified 41 circulating smoking-related miRNAs, 38 of which reversed after cessation. Cigarette smoke alters miRNA pathways involved in angiogenesis, COPD, inflammatory bowel disease, psychiatric disorders, and skin aging. These miRNA profiles may support non-invasive risk stratification, diagnosis, and treatment monitoring, although further validation and standardization are required. Conclusion: This review integrates epidemiological, experimental, and clinical findings to provide a comprehensive framework for understanding smoking‑induced miRNome remodeling and its contribution to disease burden, while identifying critical knowledge gaps for future research.