# FBXO10 Drives Hepatocellular Carcinoma Proliferation via K63-Linked Ubiquitination and Stabilization of FRMPD1

## TL;DR

This study identifies FBXO10 as a key driver of liver cancer by stabilizing FRMPD1 through ubiquitination, offering new insights for diagnosis and treatment.

## Contribution

The paper reveals a novel FBXO10–FRMPD1 interaction mechanism in hepatocellular carcinoma progression.

## Key findings

- FBXO10 is upregulated in HCC and linked to poor prognosis and advanced tumor stages.
- FBXO10 promotes HCC cell proliferation by stabilizing FRMPD1 via K63-linked ubiquitination.
- FBXO10 expression correlates with TP53 mutations and adverse clinicopathological features in HCC.

## Abstract

Aberrant ubiquitination drives hepatocellular carcinoma (HCC) progression, yet the role of FBXO10—a key F-box E3 ubiquitin ligase component—remains uncharacterized. Through bioinformatics analyses and functional validation, we establish FBXO10 as a critical oncogenic driver in HCC. Transcriptomic data from public databases (TIMER, UALCAN, GEO) revealed significant FBXO10 upregulation in HCC tissues, with elevated expression predicting advanced tumor stage, metastasis, and reduced survival. Functionally, FBXO10 silencing suppressed HCC cell proliferation while its overexpression promoted tumor growth. Mechanistic studies revealed that FBXO10 directly interacts with FRMPD1 to mediate its K63-linked polyubiquitination and stabilization, independent of transcriptional regulation. FRMPD1 restoration rescued FBXO10-mediated proliferation, confirming its role as the key downstream effector. Clinically, FBXO10 expression correlated with TP53 mutations and adverse clinicopathological features. Our findings reveal a novel FBXO10–FRMPD1 axis promoting hepatocarcinogenesis through post-translational stabilization, positioning FBXO10 as both a prognostic biomarker and therapeutic target in HCC.