Evidence map›Paper›PMID 41193183›Full record

ArticleJournal for immunotherapy of cancer2025

USP2-mediated PPARγ stabilization promotes hepatocellular carcinoma progression and M2 macrophage polarization via oleic acid.

Jing Cao, Kui Chen, Kuan Hu, Xingyu Mi, Yilin Pan, Desheng Xiao, Shuang Liu, Liang Xiao, Ledu Zhou, Yongguang Tao and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Crosstalk BetweenCancers · 2026
    Review
  5. Review
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

11 authors.

Jing CaoDepartment of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Kui ChenDepartment of Liver Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Kuan HuDepartment of Liver Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Xingyu MiDepartment of Liver Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Yilin PanDepartment of Liver Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Desheng XiaoDepartment of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Shuang LiuDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Liang XiaoDepartment of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China xiaoliang@csu.edu.cn zhould@csu.edu.cn taoyong@csu.edu.cn tangjn@csu.edu.cn.
Ledu ZhouDepartment of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China xiaoliang@csu.edu.cn zhould@csu.edu.cn taoyong@csu.edu.cn tangjn@csu.edu.cn.
Yongguang TaoCancer Research Institute and School of Basic Medicine, Central South University, Changsha, China xiaoliang@csu.edu.cn zhould@csu.edu.cn taoyong@csu.edu.cn tangjn@csu.edu.cn.
Jianing TangDepartment of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China xiaoliang@csu.edu.cn zhould@csu.edu.cn taoyong@csu.edu.cn tangjn@csu.edu.cn.ORCID http://orcid.org/0000-0003-2707-597X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHepatocellular carcinoma (HCC) is an aggressive liver cancer with poor prognosis. Deubiquitinating enzymes (DUBs) are critical regulators of tumor progression, yet the functional significance of DUBs in HCC remains poorly understood.

methodsHCC patient-derived organoids (PDOs), HCC cell lines and animal models were used to evaluate the anticancer responses of ubiquitin-specific protease (USP)2 inhibition. We analyzed the correlation of USP2 expression and immune cells infiltration using single-cell RNA sequencing and flow cytometry analysis. Mechanistically, we established an in vitro co-culture system and analyzed metabolic data to find out the bridge between tumor cell USP2 and macrophage in the microenvironment. Immunofluorescence, co-immunoprecipitation, CUT&RUN, ELISA, and mass spectrometry were conducted to explore the molecular pathway.

resultsWe found that the inhibitor (ML364) targeting USP2 shows effective anticancer responses against HCC PDOs. Targeting USP2 significantly inhibits lipid metabolism of HCC and induces cell ferroptosis. Single-cell RNA sequencing analysis and multiplex immunohistochemistry analysis indicated that high expression of USP2 in HCC was associated with the infiltration of M2 macrophage. Mechanistically, USP2 deubiquitinates and stabilizes peroxisome proliferator-activated receptor gamma (PPARγ) via removing the K48-linked ubiquitin chain at the K142 site. PPARγ promotes the transcription of fatty acid biosynthesis-related genes (ATP-citrate lyase, acetyl-CoA carboxylase and ACSS2) and de novo synthesis of fatty acids including oleic acid. HCC cell-derived oleic acid promotes M2 macrophage polarization by enhancing the fatty acid oxidation of macrophages. Polarized M2 macrophages further secrete interleukin-10, which created an IL-10/STAT3/USP2 positive-feedback loop to activate USP2 expression continuously.

conclusionOur data suggest that USP2, a key molecule mediating the interaction between HCC cells and tumor-associated macrophages, may be a promising therapeutic target for HCC.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsMacrophagesOleic AcidPPAR gammaUbiquitin ThiolesteraseAnimalsCell Line, TumorDisease ProgressionHumansMiceOleic AcidPPAR gammaUbiquitin ThiolesteraseUSP2 protein, humanImmunotherapyMacrophage

Identifiers

PMID41193183
PMCPMC12588028

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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 Socratic graph.