MicroRNA-regulated signaling and tumor microenvironment modulation in lung cancer: mechanistic insights and translational opportunities

Lung cancer is the leading cause of cancer-related mortality worldwide. Its clinical complexity and resistance to therapy arise largely from the profound heterogeneity of its molecular signaling networks. Recent research has highlighted the significant role that microRNAs (miRNAs), small endogenous non-coding RNAs, play in the development and progression of lung cancer via diverse molecular mechanisms. miRNAs can act as either oncogenes, promoting cancer progression, or as tumor suppressors, inhibiting tumor growth. Their dysregulation has been closely linked to several fundamental characteristics of lung cancer, including sustained proliferation, immune evasion, resistance to programmed cell death, aggressive invasion and metastasis, angiogenesis, and metabolic reprogramming. Each of these features contributes significantly to the aggressiveness and therapeutic resistance of lung cancer. This review examines current insights into the roles of miRNAs in lung cancer, outlining the mechanisms by which miRNA-mediated signaling pathways drive tumorigenesis and influence the tumor microenvironment. Furthermore, it explores the emerging potential of miRNAs in lung cancer diagnostics and therapeutics. By providing insights into the molecular functions of miRNAs, this review elucidates the promising prospects of miRNAs as biomarkers for early diagnosis and targets for novel therapeutic strategies in lung cancer.