Isoliquiritigenin Suppresses Oral Squamous Cell Carcinoma Progression by Targeting FABP5-Mediated Lipid Metabolism:Association with the circPOLB/miR-548ae-3p/C-MYC AxisOA

Objectives:Oral squamous cell carcinoma(OSCC)is a common and deadly cancer affecting the oral cavity.This study aims to explore the regulatory role and molecular mechanism of miR-548ae-3p in OSCC proliferation,invasion,and lipid metabolism,as well as the therapeutic potential of isoliquiritigenin(ISL)targeting OSCC lipid metabolism.Methods:Expression levels of miR-548ae-3p were measured in OSCC cell lines and normal oral keratinocytes using real-time quantitative polymerase chain reaction.Functional assays,such as cell counting Kit-8 proliferation and Transwell invasion assays,evaluated the effects of miR-548ae-3p overexpression in CAL-27 and SCC-25 cells.Bioinformatic prediction and dual-luciferase reporter assays investigated interactions among miR-548ae-3p,hsa_circRNA_0001794(circPOLB),and cellular myelocytomatosis oncogene(c-MYC).Lipid metabolism was assessed using lipid droplet staining,fatty acid oxidation assays,total fatty acids and palmitic acid quantification,and fatty acid-binding protein 5(FABP5)expression analysis.The inhibitory effects of ISL on OSCC lipid metabolism and invasiveness were also examined.Results:MiR-548ae-3p was downregulated in OSCC cells compared to normal keratinocytes(n=3,p<0.001).miR-548ae-3p overexpression inhibited the proliferation and invasion of CAL-27 and SCC-25 cells(n=3,p<0.001).CircPOLB functions as a molecular sponge for miR-548ae-3p,which in turn targets c-MYC,a key oncogene.MiR-548ae-3p overexpression reduced lipid droplet accumulation,fatty acid oxidation,total fatty acid content,and intracellular palmitic acid levels,accompanied by downregulation of FABP5(n=3,p<0.001).Furthermore,ISL treatment decreased FABP5 expression,fatty acid metabolism,and invasive capacity of OSCC cells(n=3,p<0.001),supporting its potential as a therapeutic agent.Conclusions:MiR-548ae-3p displays tumorsuppressive activity in OSCC,restraining proliferation,invasion,and fatty-acid metabolism through engagement of the circPOLB/c-MYC axis and is associated with reduced FABP5 expression.Targeting lipid metabolism using agents like ISL could be a promising approach for treating OSCC.