The Role of microRNAs in Lung Cancer: Mechanisms, Diagnostics and Therapeutic Potential

Abstract

MicroRNAs (miRNAs) are small RNA molecules that do not have coding functions but play essential roles in various biological processes. In lung cancer, miRNAs affect the processes of tumor initiation, progression, metastasis, and resistance to treatment by regulating gene expression. Tumor-suppressive miRNAs inhibit oncogenic pathways, while oncogenic miRNAs, known as oncomiRs, promote malignant transformation and tumor growth. These dual roles position miRNAs as critical players in lung cancer biology. Studies in recent years have shown the significant potential of miRNAs as both prognostic and diagnostic biomarkers. Circulating miRNAs in plasma or sputum demonstrate specificity and sensitivity in detecting early-stage lung cancer. Liquid biopsy-based miRNA panels distinguish malignant from benign lesions, and specific miRNA expression patterns correlate with disease progression, response to treatment, and overall survival. Therapeutically, miRNAs hold promise for targeted interventions. Strategies such as miRNA replacement therapy using mimics for tumor-suppressive miRNAs and inhibition of oncomiRs with antagomiRs or miRNA sponges have shown preclinical success. Key miRNAs, including the let-7 family, miR-34a, and miR-21, are under investigation for their therapeutic potential. It should be emphasized that delivery difficulties, side effects, and limited stability of therapeutic miRNA molecules remain obstacles to their clinical use. This article examines the roles of miRNAs in lung cancer by indicating their mechanisms of action, diagnostic significance, and therapeutic potential. By addressing current limitations, miRNA-based approaches could revolutionize lung cancer management, offering precise, personalized, and minimally invasive solutions for diagnosis and treatment.

Keywords: diagnostic biomarkers; liquid biopsy; lung cancer; microRNAs; personalized medicine; prognostic biomarkers; targeted therapy.

Figure 1

Biogenesis of miRNA. In the nucleus, primary miRNA is generated via RNA polymerase II. Afterward, Drosha and DGCR8 trim pri-miRNA, resulting in the formation of pre-miRNA, which is exported by Exportin-5 to the cytoplasm. There, the Dicer complex, consisting of TAR RNA-binding protein (TRBP) and protein activator of interferon-induced protein kinase (PACT), regulates miRNA maturation. Finally, the RNA-induced silencing complex (RISC) complex is created and binds to Argonaute (AGO) protein. Mature RISC complex attaches to target mRNA at complementary locations, causing translational inhibition or target destruction [15].

Figure 2

Schematic visualization of the oncogenic activity of miR-137 in lung cancer progression. miR-137 is transcriptionally activated by Slug, which binds to the E-box in its promoter. Once expressed, miR-137 suppresses the TFAP2C, leading to increased cancer cell invasion and progression. Clinical data support this mechanism, as low Slug and miR-137 expression, along with high TFAP2C levels, correlate with better survival rates in lung adenocarcinoma patients [47].