Evidence map›Paper›PMID 40067532›Full record

ArticleMedical oncology (Northwood, London, England)2025

FBXO32 ubiquitination of SUFU promotes progression and lenvatinib resistance in hepatocellular carcinoma via hedgehog signaling.

Shunyi Wang, Rui Peng, Chen Chen, Daoyuan Tu, Jun Cao, Bingbing Su, Songsong Fan, Yangyang Miao, Chi Zhang, Guoqing Jiang and 2 more

Abstract read
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In one paragraph

Article in Medical oncology (Northwood, London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Shunyi Wang *Department of Hepatobiliary Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
Rui Peng *Department of Hepatobiliary Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
Chen Chen *Department of Hepatobiliary Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
Daoyuan Tu *Department of Hepatobiliary Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
Jun CaoDepartment of Hepatobiliary Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
Bingbing SuDepartment of Hepatobiliary Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
Songsong FanDepartment of Hepatobiliary Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
Yangyang MiaoDepartment of Hepatobiliary Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
Chi ZhangDepartment of Hepatobiliary Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
Guoqing JiangDepartment of Hepatobiliary Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
Shengjie JinDepartment of Hepatobiliary Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
Dousheng BaiDepartment of Hepatobiliary Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China. drbaidousheng@yzu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lenvatinib is a prevalent treatment for hepatocellular carcinoma (HCC), yet resistance to the drug significantly limits its effectiveness. This study investigates the role of FBXO32 (F-Box Protein 32) in HCC progression and lenvatinib resistance. Methods: We utilized the GSE211850 and GSE46408 datasets to identify an E3 ubiquitin ligase that is highly expressed in both lenvatinib-resistant HCC cells and HCC tissues. The expression and clinical relevance of this E3 ubiquitin ligase were further validated using lenvatinib-resistant HCC cells, online databases, and HCC clinical tissue samples. The phenotype was verified by cell and animal experiments. Techniques such as RNA sequencing, western blotting, immunofluorescence, Co-immunoprecipitation (Co‑IP), Ubiquitination, and cycloheximide (CHX) chase assay reveal the mechanism. FBXO32 is highly expressed in both lenvatinib-resistant HCC cells and HCC tissues. High FBXO32 expression correlated with increased ALT, AFP levels, larger tumors, and advanced TNM stages, serving as an independent risk factor for overall survival (OS) and recurrence-free survival (RFS). Functional assays demonstrated that FBXO32 overexpression enhanced cell proliferation, stemness, apoptosis resistance, and lenvatinib resistance, while knockdown had opposing effects. KEGG enrichment analysis indicated a link between FBXO32 and the Hedgehog signaling pathway. FBXO32-mediated degradation of SUFU, a Hedgehog pathway inhibitor, activated this pathway. Inhibiting Hedgehog signaling counteracted FBXO32's impact on HCC growth and resistance. Conclusion: FBXO32 is a critical marker for lenvatinib efficacy and HCC prognosis, suggesting that targeting FBXO32 or the Hedgehog pathway could provide innovative strategies for overcoming lenvatinib resistance in HCC.

Indexed as

Carcinoma, HepatocellularDrug Resistance, NeoplasmHedgehog ProteinsLiver NeoplasmsMuscle ProteinsPhenylurea CompoundsQuinolinesRepressor ProteinsSKP Cullin F-Box Protein LigasesAnimalsAntineoplastic AgentsCell Line, TumorCell ProliferationDisease ProgressionFemaleHumansAntineoplastic AgentsFBXO32 protein, humanHedgehog ProteinslenvatinibMuscle ProteinsPhenylurea CompoundsQuinolinesRepressor ProteinsSKP Cullin F-Box Protein LigasesFBXO32Hedgehog signaling pathwayHepatocellular carcinomaLenvatinib resistanceSUFUUbiquitination

Identifiers

PMID40067532

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.