Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Advanced glycation end products (AGEs) and their receptor receptor for AGEs (RAGE) promote tumor progression via activation of the nuclear factor-kappa B (NF-?B) signaling pathway. Although 3-Hydroxyflavone exhibits anticancer properties, its role in oral squamous cell carcinoma (OSCC) and its interaction with the AGEs/RAGE/NF-?B axis remain unclear. Objectives: This study investigated whether 3-Hydroxyflavone inhibits OSCC by modulating miR-142-5p within the AGEs/RAGE/NF-?B axis. Methods: The expression of p65 and miR-142-5p was analyzed in both OSCC tissues and Tca8113 cells. TargetScan prediction and dual-luciferase reporter assays confirmed that p65 is a direct target of miR-142-5p. The effects of 3-Hydroxyflavone on OSCC cells were evaluated using MTT and colony formation assays. Additionally, immunohistochemistry was performed to assess p65 expression in tumor tissues, and Kaplan-Meier analysis was used to evaluate patient survival. Results: OSCC tissues showed increased p65 nuclear translocation and decreased miR-142-5p levels. The miR-142-5p directly inhibited p65. The 3-Hydroxyflavone treatment suppressed OSCC cell proliferation and colony formation by upregulating miR-142-5p and inhibiting the AGEs/RAGE/NF-?B pathway. High p65 expression correlated with poor survival, while 3-Hydroxyflavone treatment reduced p65 and improved survival. Conclusion: The 3-Hydroxyflavone inhibits OSCC proliferation and enhances survival by upregulating miR-142-5p, which suppresses AGEs/RAGE/NF-?B signaling, suggesting a novel therapeutic strategy.