Evidence mapPaperPMID 41345704Full record

ArticleJournal of experimental & clinical cancer research : CR2025

Lactylation-driven KRT19 promotes non-small cell lung cancer progression by suppressing cellular senescence.

Cai Zhang, Yue Du, Yangyang Ji, Xiaoxiao Ye, Jingyao Lian, Haonan Zhou, Zihan Gao, Huiping Xu, Yuehan Tang, Yanhong Fan and 1 more

Abstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

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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

3 citing papers in PubMed.

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4 · The record

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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.

Cai Zhang *Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. zhangcai9394@zzu.edu.cn.
Yue Du *Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Yangyang JiDepartment of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Xiaoxiao YeDepartment of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Jingyao LianDepartment of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Haonan ZhouDepartment of Clinical Laboratory Sciences, The First Clinical Medical College of Zhengzhou University, Zhengzhou, 450052, China.
Zihan GaoDepartment of Clinical Laboratory Sciences, The First Clinical Medical College of Zhengzhou University, Zhengzhou, 450052, China.
Huiping XuDepartment of Clinical Laboratory Sciences, The First Clinical Medical College of Zhengzhou University, Zhengzhou, 450052, China.
Yuehan TangDepartment of Clinical Laboratory Sciences, The First Clinical Medical College of Zhengzhou University, Zhengzhou, 450052, China.
Yanhong FanDepartment of Clinical Laboratory Sciences, The First Clinical Medical College of Zhengzhou University, Zhengzhou, 450052, China.
Lu ZhengDepartment of Blood Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

Funding

Henan Provincial Science and Technology Research and Development Joint Fund Program 242301420075Key scientific research project plan of colleges and universities in Henan Province 25A320006National Natural Science Foundation of China 82573158
6 · The paper itself

Abstract

backgroundCellular senescence provides a protective barrier against tumorigenesis. However, the detailed mechanisms underlying tumor cells bypass senescence to malignant progression of non-small cell lung cancer (NSCLC) are still poorly understood.

methodsIn this study, we assessed the impact of KRT19 on NSCLC using xenograft tumor models, EdU, CCK8, colony formation and transwell assay. We performed chromatin immunoprecipitation sequencing and dual luciferase reporter assay to explore the mechanism through which H3K18 lactylation (H3K18la) mediated KRT19. The mechanism underlying KRT19 regulated p21-driven cellular senescence was explored by senescence-associated β-galactosidase staining, flow cytometry and further identified by RNA sequencing, mass spectrometry, immunofluorescence, co-immunoprecipitation and protein ubiquitination assay. The clinical significance of H3K18la/KRT19/p21 was determined by immunohistochemistry in human NSCLC specimens and bioinformatics analysis of TCGA database and Kaplan-Meier method. We evaluated the effects of KRT19 inhibition and anti-PD-1 on NSCLC growth and immune infiltration using xenograft tumor models, flow cytometry and CIBERSORT.

resultsOur study revealed that elevated expression of KRT19 was correlated with poor prognosis of NSCLC patients and exhibited oncogenic activity in NSCLC. Mechanistically, lactate-derived H3K18la activated the transcription of KRT19 via directly binding to its promoter. KRT19 blocked the transcriptional activation of p21 by p53, alternatively, KRT19 also interacted with MYH9 to facilitate ubiquitination of p21 at K16. More significantly, blockade of KRT19 potently enhanced the cytotoxic function of tumor-infiltrating CD8

conclusionOur study emphasizes the importance of lactylation-driven KRT19 for overriding senescence and promoting NSCLC progression, reinforcing the potential of combination therapy strategies with KRT19 inhibitors to yield favorable responses in patients with NSCLC.

Indexed as

Carcinoma, Non-Small-Cell LungCellular SenescenceKeratin-19Lung NeoplasmsAnimalsCell Line, TumorCell ProliferationDisease ProgressionFemaleGene Expression Regulation, NeoplasticHistonesHumansMaleMiceMice, NudePrognosisHistonesKeratin-19KRT19 protein, humanCellular senescenceKRT19LactylationNon-small cell lung cancerP21Ubiquitination

Identifiers

PMID41345704
PMCPMC12802155

What Socratic holds

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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 Socratic graph.