Clinical significance of miRNAs and exosomal miRNAs in non-small cell lung cancer: diagnostic, prognostic, and therapeutic perspectives.

Lung cancer is the most frequently diagnosed malignancy and the leading cause of cancer-related mortality worldwide, with approximately 85% of cases classified as non-small cell lung cancer (NSCLC). Despite significant advances in diagnostic techniques and therapeutic strategies, including immunotherapy and targeted therapies, the prognosis of lung cancer remains poor, with an overall 5-year survival rate of approximately 22%. MicroRNAs (miRNAs) are small, single-stranded, non-coding RNA molecules that regulate gene expression at the post-transcriptional level and play critical roles in key biological processes, such as proliferation, apoptosis, migration, and invasion. miRNAs can function as oncogenes (oncomiRs) or tumor suppressors (TS-miRs), and their dysregulation is frequently observed in various malignancies, including NSCLC. Owing to their remarkable stability in serum and plasma, miRNAs have emerged as promising non-invasive biomarkers for the diagnosis and prognosis of NSCLC. In particular, exosomal miRNAs are encapsulated within a lipid bilayer that protects them from enzymatic degradation, thereby further enhancing their utility as liquid biopsy components and as potential biomarkers and therapeutic targets. Moreover, a single miRNA can regulate multiple target genes, highlighting their promise as therapeutic targets. This review summarizes the diagnostic, prognostic, predictive, and therapeutic potential of tissue-derived, circulating, and exosomal miRNAs in NSCLC and discusses the major challenges limiting the clinical translation of miRNA-based biomarkers and therapeutics.