Elucidating the Role of let-7d-5p and OLR1 in Progression and Prognosis of Oral Squamous Cell Carcinoma via FAK/P53 Signaling axis

Abstract Purpose: This study investigates the role of let-7d-5p microRNA (miRNA) and its target gene OLR1 in oral squamous cell carcinoma (OSCC), focusing on their implications in tumor progression, metastasis and potential as therapeutic targets. Despite advances in OSCC diagnosis and treatment, the five-year survival rate remains low, underscoring the need for improved biomarkers and therapeutic strategies. We aim to elucidate the regulatory functions of let-7d-5p and OLR1 in OSCC pathogenesis. Methods: Employing next-generation sequencing and bioinformatic tools, we profiled differentially expressed miRNAs in metastatic OSCC cell lines, identifying let-7d-5p as a key downregulated miRNA and OLR1 as a novel target of let-7d-5p. We validated this interaction using luciferase reporter assays and studied the biological effects of modulating let-7d-5p and OLR1 expression on OSCC cell proliferation, migration, invasion and stemness. Additionally, we analyzed clinical data to establish the relevance of OLR1 expression in OSCC prognosis. Results: Our findings reveal let-7d-5p as a potent suppressor of OSCC metastasis, primarily by targeting and downregulating OLR1. OLR1 -silencing reduced OSCC cell invasiveness, migration, and stemness, implicating its prominent role in tumor progression. Mechanistically, let-7d-5p modulates a signaling cascade involving FAK, SRC, PAXILLIN, and P53, influencing cellular apoptosis and chemoresistance. Clinically, elevated OLR1 expression significantly correlates with advanced OSCC stages and poorer survival rates, highlighting its potential as a prognostic marker and therapeutic target. Conclusion: Our study uncovers the significance of the let-7d-5p-OLR1 axis in OSCC pathogenesis, offering novel insights for future therapeutic interventions.