Evidence mapPaperPMID 38760896Full record

ArticleClinical and translational medicine2024

DNA-PKcs/AKT1 inhibits epithelial-mesenchymal transition during radiation-induced pulmonary fibrosis by inducing ubiquitination and degradation of Twist1.

Ziyan Yan, Jiaojiao Zhu, Yuhao Liu, Zhongqiu Li, Xinxin Liang, Shenghui Zhou, Yifan Hou, Huixi Chen, Lin Zhou, Ping Wang and 5 more

Abstract read
In one paragraph

Article in Clinical and translational medicine, 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.

  1. Article
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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

15 authors.

Ziyan YanBeijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China.
Jiaojiao ZhuBeijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China.
Yuhao LiuBeijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China.
Zhongqiu LiState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Xinxin LiangHengyang Medical College, University of South China, Hengyang, China.
Shenghui ZhouHengyang Medical College, University of South China, Hengyang, China.
Yifan HouCollege of Life Sciences, Hebei University, Baoding, China.
Huixi ChenHengyang Medical College, University of South China, Hengyang, China.
Lin ZhouBeijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China.
Ping WangBeijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China.
Xingkun AoHengyang Medical College, University of South China, Hengyang, China.
Shanshan GaoBeijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China.
Xin HuangBeijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China.
Ping-Kun ZhouBeijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China.
Yongqing GuBeijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China.ORCID 0000-0002-2211-8195

Funding

National Natural Science Foundation of China 31470827National Natural Science Foundation of China 32171238National Natural Science Foundation of China 81773359National Natural Science Foundation of China 82073488National Natural Science Foundation of China 82230108National Natural Science Foundation of China 82273568
6 · The paper itself

Abstract

introductionRadiation-induced pulmonary fibrosis (RIPF) is a chronic, progressive, irreversible lung interstitial disease that develops after radiotherapy. Although several previous studies have focused on the mechanism of epithelial-mesenchymal transition (EMT) in lung epithelial cells, the essential factors involved in this process remain poorly understood. The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) exhibits strong repair capacity when cells undergo radiation-induced damage; whether DNA-PKcs regulates EMT during RIPF remains unclear.

objectivesTo investigate the role and molecular mechanism of DNA-PKcs in RIPF and provide an important theoretical basis for utilising DNA-PKcs-targeted drugs for preventing RIPF.

methodsDNA-PKcs knockout (DPK

resultsThe expression of DNA-PKcs is low in pulmonary fibrosis (PF) patients. DNA-PKcs deficiency significantly exacerbated RIPF by promoting EMT in lung epithelial cells. Mechanistically, DNA-PKcs deletion by shRNA or inhibitor NU7441 maintained the protein stability of Twist1. Furthermore, AKT1 mediated the interaction between DNA-PKcs and Twist1. High Twist1 expression and EMT-associated changes caused by DNA-PKcs deletion were blocked by insulin-like growth factor-1 (IGF-1), an AKT1 agonist. The radioprotective drug VND3207 prevented IR-induced EMT and alleviated RIPF in mice by stimulating the kinase activity of DNA-PKcs.

conclusionOur study clarified the critical role and mechanism of DNA-PKcs in RIPF and showed that it could be a potential target for preventing RIPF.

Indexed as

DNA-Activated Protein KinaseEpithelial-Mesenchymal TransitionNuclear ProteinsProto-Oncogene Proteins c-aktPulmonary FibrosisTwist-Related Protein 1AnimalsDNA-Binding ProteinsHumansMiceMice, KnockoutUbiquitinationAkt1 protein, mouseDNA-Activated Protein KinaseDNA-Binding ProteinsNuclear ProteinsPRKDC protein, humanPrkdc protein, mouseProto-Oncogene Proteins c-aktTWIST1 protein, humanTwist1 protein, mouseTwist-Related Protein 1DNA‐PKcsepithelial–mesenchymal transitionradiation‐induced pulmonary fibrosisTwist1VND3207

Identifiers

PMID38760896
PMCPMC11101672

What Socratic holds

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LicenceCC BY
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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 Socratic graph.