Evidence map›Paper›PMID 40075132›Full record

ArticleScientific reports2025

Proteasome inhibition induces DNA methylation alteration by attenuating the synthesis of DNA methyltransferase 1 and 3B in colorectal cancer.

Wenwen Zhou, Yuling Sheng, Dingxue Hu, Yunyun An, Mengqi Yang, Wanqiu Wang, Shiva Basnet, Jingyu Yan, Shuxia Zhang, Qi Liu and 5 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Wenwen Zhou *Key University Laboratory of Metabolism and Health of Guangdong, Biochemistry Department, School of Medicine, Southern University of Science and Technology, 1088 Xueyuan Avenue, Shenzhen, 518055, Guangdong, People's Republic of China.
Yuling Sheng *Key University Laboratory of Metabolism and Health of Guangdong, Biochemistry Department, School of Medicine, Southern University of Science and Technology, 1088 Xueyuan Avenue, Shenzhen, 518055, Guangdong, People's Republic of China.
Dingxue Hu *Institute of Cancer Research, Shenzhen Bay Laboratory, Gaoke Innovation Center, Room A1921, Guangming District, Shenzhen, 518132, People's Republic of China.
Yunyun AnInstitute of Cancer Research, Shenzhen Bay Laboratory, Gaoke Innovation Center, Room A1921, Guangming District, Shenzhen, 518132, People's Republic of China.
Mengqi YangInstitute of Cancer Research, Shenzhen Bay Laboratory, Gaoke Innovation Center, Room A1921, Guangming District, Shenzhen, 518132, People's Republic of China.
Wanqiu WangInstitute of Cancer Research, Shenzhen Bay Laboratory, Gaoke Innovation Center, Room A1921, Guangming District, Shenzhen, 518132, People's Republic of China.
Shiva BasnetKey University Laboratory of Metabolism and Health of Guangdong, Biochemistry Department, School of Medicine, Southern University of Science and Technology, 1088 Xueyuan Avenue, Shenzhen, 518055, Guangdong, People's Republic of China.
Jingyu YanKey University Laboratory of Metabolism and Health of Guangdong, Biochemistry Department, School of Medicine, Southern University of Science and Technology, 1088 Xueyuan Avenue, Shenzhen, 518055, Guangdong, People's Republic of China.
Shuxia ZhangKey University Laboratory of Metabolism and Health of Guangdong, Biochemistry Department, School of Medicine, Southern University of Science and Technology, 1088 Xueyuan Avenue, Shenzhen, 518055, Guangdong, People's Republic of China.
Qi LiuKey University Laboratory of Metabolism and Health of Guangdong, Biochemistry Department, School of Medicine, Southern University of Science and Technology, 1088 Xueyuan Avenue, Shenzhen, 518055, Guangdong, People's Republic of China.
Yunze LiKey University Laboratory of Metabolism and Health of Guangdong, Biochemistry Department, School of Medicine, Southern University of Science and Technology, 1088 Xueyuan Avenue, Shenzhen, 518055, Guangdong, People's Republic of China.
Yi TanKey University Laboratory of Metabolism and Health of Guangdong, Biochemistry Department, School of Medicine, Southern University of Science and Technology, 1088 Xueyuan Avenue, Shenzhen, 518055, Guangdong, People's Republic of China.
Jing GaoPeking University Shenzhen Hospital, 1120 Lianhua Road, Shenzhen, 516473, Guangdong, People's Republic of China.
Kun SunInstitute of Cancer Research, Shenzhen Bay Laboratory, Gaoke Innovation Center, Room A1921, Guangming District, Shenzhen, 518132, People's Republic of China. sunkun@szbl.ac.cn.
Changzheng DuCancer Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, 168 Litang Road, Changping District, Beijing, 102218, People's Republic of China. dzza04606@btch.edu.cn.

Funding

National Natural Science Foundation of China 32170590
6 · The paper itself

Abstract

Proteasome is an essential organelle responsible for maintaining cellular protein homeostasis, but its relationship with DNA methylation remains unknown. In this study, we assessed DNA methylation of colorectal cancer (CRC) cells following treatment with proteasome inhibitors, and investigated the underlying mechanism of DNA methylation changes and the biological effects on CRC cells. We established that inhibition of proteasome leads to significant alterations in DNA methylation profile in CRC by suppressing the synthesis of DNA methyltransferases (DNMTs). We found that treating CRC cells with proteasome inhibitors results in attenuated translation of DNMT1 and DNMT3B, mediated by the inactivation of AKT and mammalian target of rapamycin (mTOR), which is dependent on the accumulation of p300, an acetyltransferase that inhibits AKT through acetylation modification. Furthermore, we demonstrated that downregulation of DNMT1 and DNMT3B confers protection against proteasome inhibitor treatment, potentially through reprogramming the transcriptome of CRC cells, highlighting the significant role of DNMTs in response to disruptions in protein homeostasis. Interestingly, it appears that the proteasome inhibitor-induced downregulation of DNMT1 and DNMT3B is specific to CRC. Altogether, our findings reveal an epigenetic effect of proteasome on DNA methylation in CRC through its regulation of DNA methyltransferase synthesis.

Indexed as

Colorectal NeoplasmsDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA MethylationProteasome InhibitorsCell Line, TumorDNA Methyltransferase 3BGene Expression Regulation, NeoplasticHumansProteasome Endopeptidase ComplexProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3BDNMT1 protein, humanProteasome Endopeptidase ComplexProteasome InhibitorsProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesColorectal cancerDNA methyltransferaseProteasome

Identifiers

PMID40075132
PMCPMC11903776

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.