Evidence map›Paper›PMID 39179546›Full record

ArticleCell death & disease2024

Hexokinase HK3-mediated O-GlcNAcylation of EP300: a key regulator of PD-L1 expression and immune evasion in ccRCC.

Wei Zhang, Enyang Zhao, Zhuolun Li, Weiyang Liu, Jinpeng Wang, Wenbin Hou, Nan Zhang, Yang Yu, Xuedong Li, Bosen You

Abstract read
In one paragraph

Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 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

10 authors.

Wei Zhang *Department of Urology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Enyang Zhao *Department of Urology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Zhuolun Li *Department of Urology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Weiyang Liu *Department of Urology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Jinpeng WangDepartment of Urology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Wenbin HouDepartment of Urology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Nan ZhangDepartment of Urology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Yang YuDepartment of Urology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Xuedong LiDepartment of Urology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. h06370@hrbmu.edu.cn.ORCID 0000-0002-1872-4213
Bosen YouDepartment of Urology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. h07101@hrbmu.edu.cn.ORCID 0000-0003-3350-2464

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Clear cell renal cell carcinoma (ccRCC) demonstrates enhanced glycolysis, critically contributing to tumor development. Programmed death-ligand 1 (PD-L1) aids tumor cells in evading T-cell-mediated immune surveillance. Yet, the specific mechanism by which glycolysis influences PD-L1 expression in ccRCC is not fully understood. Our research identified that the glycolysis-related gene (GRG) HK3 has a unique correlation with PD-L1 expression. HK3 has been identified as a key regulator of O-GlcNAcylation in ccRCC. O-GlcNAcylation exists on the serine 900 (Ser900) site of EP300 and can enhance its stability and oncogenic activity by preventing ubiquitination. Stably expressed EP300 works together with TFAP2A as a co-transcription factor to promote PD-L1 transcription and as an acetyltransferase to stabilize PD-L1 protein. Furthermore, ccRCC exhibits interactive dynamics with tumor-associated macrophages (TAMs). The uridine 5'-diphospho-N-acetylglucosamine (UDP-GlcNAc), which serves as a critical substrate for the O-GlcNAcylation process, facilitates TAMs polarization. In ccRCC cells, HK3 expression is influenced by IL-10 secreted by M2 TAMs. Our study elucidates that HK3-mediated O-GlcNAcylation of EP300 is involved in tumor immune evasion. This finding suggests potential strategies to enhance the efficacy of immune checkpoint blockade therapy.

Indexed as

B7-H1 AntigenCarcinoma, Renal CellE1A-Associated p300 ProteinHexokinaseKidney NeoplasmsAnimalsCell Line, TumorGene Expression Regulation, NeoplasticGlycolysisHumansImmune EvasionMiceTumor-Associated MacrophagesB7-H1 AntigenCD274 protein, humanE1A-Associated p300 ProteinEP300 protein, humanHexokinase

Identifiers

PMID39179546
PMCPMC11343739

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Registered trials

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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.