Abstract
Pancreatic cancer (PC) remains one of the most lethal malignancies worldwide, characterized by late diagnosis, rapid progression, and poor therapeutic response. Despite incremental advances, survival rates remain dismal, underscoring the urgent need for innovative diagnostic and therapeutic strategies. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post-transcriptionally, and they have emerged as critical modulators of PC pathogenesis. They influence key oncogenic and tumor-suppressive pathways including KRAS, NF-κB, and AKT/STAT3. Dysregulated miRNAs such as miR-21 and miR-155 drive tumor proliferation, epithelial–mesenchymal transition, and chemoresistance. Conversely, tumor-suppressive miRNAs like miR-34a inhibit these processes, highlighting their dual biological roles. Mounting evidence supports the value of circulating and extracellular vesicle-associated miRNAs in distinguishing PC from benign lesions. Integrated biomarker panels combining miRNAs with CA19-9 have achieved sensitivities and specificities exceeding 90%, outperforming conventional assays. Furthermore, machine learning models have enhanced the predictive power of miRNA signatures for personalized diagnosis. Therapeutically, miRNA modulation offers novel opportunities. Strategies include restoring tumor-suppressive miRNAs or inhibiting oncogenic ones using antagomirs and delivery systems like nanoparticles and viral vectors. Emerging approaches such as CRISPR-Cas9 gene editing further expand this potential. Preclinical studies demonstrate the efficacy of miRNA-based interventions in reducing tumor growth, though clinical translation is limited by delivery challenges. In conclusion, miRNAs represent a multifaceted frontier in PC research, serving as noninvasive biomarkers and promising therapeutic targets. Continued integration of molecular biology with computational innovations is poised to accelerate the implementation of miRNA-based precision oncology.