Evidence map›Paper›PMID 41935629›Full record

ArticleJHEP reports : innovation in hepatology2026

Zinc finger protein 544 promotes hepatocellular carcinoma by generating an immunosuppressive tumor microenvironment.

Jie Tang, Ming Xu, Xilong Ou

Abstract read
In one paragraph

Article in JHEP reports : innovation in hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

3 authors.

Jie TangSoutheast University School of Medicine, Nanjing, Jiangsu, PR China; Department of Gastroenterology, Shanghai Pudong New Area People's Hospital, Shanghai, PR China.
Ming XuDepartment of Gastroenterology, Shanghai Pudong New Area People's Hospital, Shanghai, PR China.
Xilong OuDepartment of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, PR China. Electronic address: ouxilong2021@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsThis study identified zinc finger protein 544 (ZNF544) as a biomarker in hepatocellular carcinoma (HCC) and aims to delineate its functional role.

methodsThe correlation between ZNF544 expression and clinical parameters of patients with HCC (n = 50) and the malignant biological behavior of HCC cells was analyzed in vitro (n = 5/group) and in vivo (n = 10/group).

resultsZNF544 was elevated in tumors of patients with HCC (p = 0.0006). Patients with HCC exhibiting high ZNF544 expression was associated with a more advanced clinical stage (p = 0.0026) and showed greater infiltration of M2 macrophages (p = 0.0031) and Tregs (p = 0.0094). ZNF544 knockdown inhibited the pro-angiogenic ability of HCC cells (p <0.01). Increased ZNF544 expression accelerated the growth of orthotopic tumors (increased >80%, p <0.0001) and the infiltration of M2 macrophages (increased >60%, p = 0.0008) and Tregs (increased >80%, p = 0.0029) within the orthotopic tumors, and accelerated lung metastasis (number of mice with lung metastasis increased >160%). ZNF544 bound to the spermatogenesis-associated serine-rich protein 2 (SPATS2) promoter and activated its transcription, whereas SPATS2 enhanced the triosephosphate isomerase (TPI1) mRNA stability. ZNF544 promoted glycolysis in HCC cells in a SPATS2-dependent manner. SPATS2 knockdown suppressed glycolysis in HCC cells and inhibited orthotopic tumor growth, which was rescued by TPI1 overexpression. Ivermectin was identified as a pharmacological inhibitor of ZNF544, effectively suppressing the progression of HCC.

conclusionsZNF544 accelerates HCC by activating SPATS2/TPI1 and promoting glycolysis and immune escape. Targeting ZNF544, including compounds such as ivermectin, may offer a preliminary avenue for further investigation in HCC. IMPACT AND IMPLICATIONS: This research underscores the role of ZNF544-SPATS2 as a pivotal regulator of TPI1 expression in HCC. TPI1 shapes the immunosuppressive TME and accelerates growth and metastasis by promoting glycolysis and facilitating the infiltration of M2 macrophages and Tregs. Our research suggests that ZNF544 could serve as a novel biomarker for HCC, and the pharmacological inhibitor of ZNF544, ivermectin, emerges as a promising therapeutic option for HCC treatment.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsTumor MicroenvironmentAnimalsBiomarkers, TumorCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMacrophagesMaleMiceBiomarkers, TumorPrognostic markersRNA-binding proteinTranscription factorsTumor microenvironment

Identifiers

PMID41935629
PMCPMC13315681

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.