Open Access

ARTICLE

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

Liang Li^1,#, Hong Deng^2,#, Zhiyong Li², Yu Li², Lingrui Liu², Lan Xie^2,*, Yue Chen^3,*

1 Department of Stomatology, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
2 State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
3 Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China

* Corresponding Authors: Lan Xie. Email: ; Yue Chen. Email:
# These authors contributed equally to this work

Oncology Research 2026, 34(8), 27 https://doi.org/10.32604/or.2026.081109

Received 23 February 2026; Accepted 11 June 2026; Issue published 16 July 2026

Abstract

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 tumor-suppressive 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.

---

Keywords

---