FBXO5 drives hepatocellular carcinoma progression and is a target for tea polyphenol-mediated inhibition

Hepatocellular carcinoma (HCC) ranks among the leading causes of cancer-related deaths globally, with current treatments offering limited efficacy. FBXO5 has emerged as a potential oncogene in multiple cancers, yet its role in HCC remains incompletely understood. Notably, tea polyphenols (TPs) are natural compounds with known antitumor properties, but their molecular targets in HCC remain unclear. This study aims to investigate the role of FBXO5 in HCC and explore whether TPs exert their antitumor effects by targeting FBXO5.

FBXO5 expression in HCC was analyzed using The Cancer Genome Atlas (TCGA) data. Functional analysis of FBXO5 in HCC cell lines was performed using small interfering RNA (siRNA) knockdown and overexpression techniques. Cell phenotypes were assessed via Cell Counting Kit-8 (CCK-8), colony formation, scratch healing, and Transwell assays. Cells treated with varying concentrations of TPs were evaluated for effects on viability, proliferation, migration, and invasion, with FBXO5 expression changes analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot. TPs' effects were further validated in FBXO5-overexpressing cells.

FBXO5 was significantly upregulated in HCC tissues and correlated with poor patient prognosis. Silencing FBXO5 inhibited HCC cells proliferation, migration, and invasion, whereas its overexpression promoted these malignant behaviors. TPs treatment dose-dependently suppressed HCC cells viability, proliferation, and motility. TPs downregulated FBXO5 expression at both messenger RNA (mRNA) and protein levels. Overexpression of FBXO5 attenuated the antitumor effects of TPs, indicating that TPs partially inhibit HCC progression by suppressing FBXO5.

FBXO5 functions as an oncogene in HCC, and TPs may serve as potential therapeutic agents for inhibiting HCC progression by targeting FBXO5.