Evidence map›Paper›PMID 42760533›Full record

ArticleJournal of translational medicine2026

ZMIZ1 promotes aerobic glycolysis and development of hepatocellular carcinoma through inducing NOTCH1-mediated transcription of PYCR1.

Jiefeng He, Chao Zhang, Guo Chen, Hao Tang, Chunhu Mao, Gang Wu

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Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Jiefeng He *Department of General Surgery, Shanxi Bethune Hospital, Third Hospital of Shanxi Medical University, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, Shanxi, 030032, China.
Chao Zhang *Department of General Surgery, Shanxi Bethune Hospital, Third Hospital of Shanxi Medical University, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, Shanxi, 030032, China.
Guo ChenThe Affiliated Hospital, Southwest Medical University, No.25 Taiping Street, Luzhou, Sichuan, 646000, China.
Hao TangThe Affiliated Hospital, Southwest Medical University, No.25 Taiping Street, Luzhou, Sichuan, 646000, China.
Chunhu MaoDepartment of Hepatobiliary Pancreatic Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No.32, Yihuan Road, Chengdu, Sichuan, 610072, China.
Gang WuDepartment of Hepatobiliary Pancreatic Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No.32, Yihuan Road, Chengdu, Sichuan, 610072, China. wugang@med.uestc.edu.cn.

Funding

Health and Family Planning Commission of Sichuan Province No.150215Hebei Province Graduate Innovation Funding Project NO.2021-166Key Program of Department of Science and Technology of Sichuan Province No.2020YJ0450National Natural Science Foundation of China No. 81302161Shanxi Province Scholarship Program for Science and Technology Activities of Overseas Students NO.20210001Shanxi Provincial Key Laboratory of Hepatobiliary and Pancreatic Diseases Shanxi Provincial Key Laboratory of Hepatobiliary and Pancreatic Diseases
6 · The paper itself

Abstract

backgroundHepatocellular carcinoma (HCC) is characterized by profound metabolic reprogramming that promotes tumor progression. Although zinc finger MIZ-type containing 1 (ZMIZ1) has been implicated in several malignancies, its biological function and underlying mechanism in HCC remain unclear.

methodsThe expression and clinical significance of ZMIZ1 and PYCR1 were evaluated using public datasets, clinical specimens, and tissue microarrays. Gain- and loss-of-function studies, rescue experiments, xenograft models, and molecular assays were performed to investigate their biological functions and regulatory mechanisms.

resultsZMIZ1 was significantly upregulated in HCC tissues and associated with unfavorable patient outcomes. Functional studies demonstrated that ZMIZ1 promoted HCC cell proliferation, migration, tumor growth, and glycolytic metabolic reprogramming. Mechanistically, PYCR1 was identified as a critical downstream effector of ZMIZ1, and reciprocal rescue experiments confirmed that PYCR1 mediated the oncogenic effects of ZMIZ1 both in vitro and in vivo. Further analyses revealed that ZMIZ1 physically interacted with NOTCH1, enhanced its nuclear accumulation, and promoted NOTCH1-dependent transcriptional activation of PYCR1. Promoter mutation assays identified a functional NOTCH1-responsive element required for this regulation. Moreover, only wild-type PYCR1, but not a catalytically inactive mutant, restored the impaired glycolytic and proliferative phenotypes caused by ZMIZ1 depletion, indicating that PYCR1 functions in an enzyme activity-dependent manner. Finally, the ZMIZ1/NOTCH1/PYCR1 axis promoted glycolytic reprogramming through activation of PI3K/AKT signaling.

conclusionZMIZ1 promotes HCC progression by enhancing NOTCH1-mediated transcriptional activation of PYCR1, thereby driving PI3K/AKT-dependent glycolytic metabolic reprogramming. These findings identify the ZMIZ1/NOTCH1/PYCR1 signaling axis as a critical regulator of HCC progression and a potential therapeutic target for HCC.

Indexed as

Carcinoma, HepatocellularGlycolysisLiver NeoplasmsPyrroline Carboxylate ReductasesReceptor, Notch1Transcription FactorsTranscription, GeneticAerobiosisAnimalsCarcinogenesisCell Line, TumorCell MovementCell Proliferationdelta-1-Pyrroline-5-Carboxylate ReductaseGene Expression Regulation, NeoplasticHumansdelta-1-Pyrroline-5-Carboxylate ReductasePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktPyrroline Carboxylate ReductasesReceptor, Notch1Transcription FactorsAerobic glycolysisHepatocellular carcinomaNOTCH1PYCR1ZMIZ1

Identifiers

PMID42760533
PMCPMC13587418

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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.