Harnessing miR-145 in NSCLC: mechanistic roles, diagnostic-prognostic utility, and therapeutic potential

Non-small cell lung cancer (NSCLC) is responsible for most lung cancer diagnoses and causes elevated worldwide mortality rates, mostly due to late detection and the development of resistance against medicines. This review summarizes evidence regarding miR-145, a downregulated NSCLC microRNA, and emphasizes the multifaceted tumor-suppressor activity of miR-145 involving the repression of oncogenes such as c-Myc, epidermal growth factor receptor (EGFR), and octamer-binding transcription factor 4 (OCT4) to restrict cell growth, stemness, epithelial-to-mesenchymal-transition (EMT), metastasis via Phosphoinositide 3-kinases (PI3Ks)/ activation of protein kinase B (AKT, Mitogen‑activated protein kinase (MAPK), and transforming growth factor beta (TGF-β)/Smad signaling. miR-145 also exhibits potential diagnostic specificity in distinguishing NSCLC cases from controls through serum/plasma testing, with greater sensitivity/specificity in multi-miRNA sets, and prognostic value predicting resistance, survival, and disease advancement. Therapeutically, miR-145 enhances responses to chemotherapies, targeted therapies, radiotherapy, and immunotherapies by counteracting resistance networks. Utilizing novel delivery platforms, such as nanoparticles, exosomes, and chemical modifications, may overcome stability and targeting issues that exist with miRNA therapies. Through the integration of preclinical and clinical information, this review helps identify crucial research gaps, such as incompletely defined regulatory networks and the need for large-scale studies, and calls for the application of advanced techniques to expedite the integration of miR-145-based treatments with personalized NSCLC therapy for improved outcomes.