Evidence map›Paper›PMID 40484999›Full record

ArticleChinese medical journal2025

P4HA1 mediates YAP hydroxylation and accelerates collagen synthesis in temozolomide-resistant glioblastoma.

Xueru Li, Gangfeng Yu, Xiao Zhong, Jiacheng Zhong, Xiangyu Chen, Qinglong Chen, Jinjiang Xue, Xi Yang, Xinchun Zhang, Yao Ling and 9 more

Abstract read
In one paragraph

Article in Chinese medical journal, 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. Review
  3. Article
  4. 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

19 authors.

Xueru LiDepartment of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Chongqing Medical University, Chongqing 404100, China.
Gangfeng YuDepartment of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Xiao ZhongDepartment of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Chongqing Medical University, Chongqing 404100, China.
Jiacheng ZhongDepartment of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Xiangyu ChenDepartment of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Chongqing Medical University, Chongqing 404100, China.
Qinglong ChenDepartment of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Chongqing Medical University, Chongqing 404100, China.
Jinjiang XueDepartment of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Chongqing Medical University, Chongqing 404100, China.
Xi YangDepartment of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Chongqing Medical University, Chongqing 404100, China.
Xinchun ZhangDepartment of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Chongqing Medical University, Chongqing 404100, China.
Yao LingSchool of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China.
Yun XiuDepartment of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Chongqing Medical University, Chongqing 404100, China.
Yaqi DengDepartment of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Chongqing Medical University, Chongqing 404100, China.
Hongda LiDepartment of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Chongqing Medical University, Chongqing 404100, China.
Wei MoDepartment of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Chongqing Medical University, Chongqing 404100, China.
Yong ZhuSchool of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China.
Ting ZhangLaboratory of Hepatic AI Translation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Liangjun QiaoSchool of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China.
Song ChenDepartment of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Fanghui LuDepartment of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Chongqing Medical University, Chongqing 404100, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTemozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens.

methodsKey extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ.

resultsThis study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival.

conclusionP4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.

Indexed as

Adaptor Proteins, Signal TransducingCollagenDacarbazineGlioblastomaProlyl HydroxylasesTemozolomideTranscription FactorsAnimalsAntineoplastic Agents, AlkylatingCell Line, TumorCollagen Type IDrug Resistance, NeoplasmHumansHydroxylationMiceYAP-Signaling ProteinsAdaptor Proteins, Signal TransducingAntineoplastic Agents, AlkylatingCollagenCollagen Type IDacarbazineProlyl HydroxylasesTemozolomideTranscription FactorsYAP1 protein, humanYAP-Signaling ProteinsChemoresistanceCollagenGlioblastomaProlyl 4-hydroxylase subunit alpha 1TemozolomideYes-associated protein

Identifiers

PMID40484999
PMCPMC12369758

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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.