Evidence map›Paper›PMID 39500892›Full record

ArticleCell death & disease2024

Hypermethylation of CDKN2A CpG island drives resistance to PRC2 inhibitors in SWI/SNF loss-of-function tumors.

Xinghao Wang, Yajun Wang, Min Xie, Shichao Ma, Yilin Zhang, Lele Wang, Yangfeng Ge, Guobin Li, Mengxi Zhao, Sheng Chen and 3 more

Abstract read
PubMed Full text at PMC Publisher
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.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Immune checkpoint inhibitors have limited efficacy inTranslational lung cancer research · 2025
    Article
  7. Review
  8. Review
  9. The Biological Function of Genome Organization.International journal of molecular sciences · 2025
    Review
  10. Review
  11. 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

13 authors.

Xinghao WangDepartment of Thoracic Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Yajun WangBlueray Biopharma Inc., Shanghai, China.
Min XieBlueray Biopharma Inc., Shanghai, China.
Shichao MaBlueray Biopharma Inc., Shanghai, China.
Yilin ZhangBlueray Biopharma Inc., Shanghai, China.
Lele WangBlueray Biopharma Inc., Shanghai, China.
Yangfeng GeBlueray Biopharma Inc., Shanghai, China.
Guobin LiBlueray Biopharma Inc., Shanghai, China.
Mengxi ZhaoBlueray Biopharma Inc., Shanghai, China.
Sheng ChenBlueray Biopharma Inc., Shanghai, China.
Chenxi YanDepartment of Thoracic Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Hailong ZhangBlueray Biopharma Inc., Shanghai, China. crystallographer@gmail.com.
Wei SunDepartment of Thoracic Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China. petersw@tjh.tjmu.edu.cn.ORCID 0009-0002-1327-5153

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Polycomb repressive complex 2 (PRC2) catalyzes the writing of the tri-methylated histone H3 at Lys27 (H3K27me3) epigenetic marker and suppresses the expression of genes, including tumor suppressors. The function of the complex can be partially antagonized by the SWI/SNF chromatin-remodeling complex. Previous studies have suggested that PRC2 is important for the proliferation of tumors with SWI/SNF loss-of-function mutations. In the present study, we have developed an EED-directed allosteric inhibitor of PRC2 termed BR0063, which exhibits anti-proliferative properties in a subset of solid tumor cell lines harboring mutations of the SWI/SNF subunits, SMARCA4 or ARID1A. Tumor cells sensitive to BR0063 exhibited several distinct phenotypes, including cell senescence, which was mediated by the up-regulation of CDKN2A/p16. Further experiments revealed that the expression of p16 was suppressed in the BR0063-resistant cells via DNA hypermethylation in the CpG island (CGI) promoter region, rather than via PRC2 occupancy. The expression of TET1, which is required for DNA demethylation, was found to be inversely correlated with p16 CGI methylation, and this may serve as a biomarker for the prediction of resistance to PRC2 inhibitors in SWI/SNF LOF tumors.

Indexed as

CpG IslandsCyclin-Dependent Kinase Inhibitor p16DNA MethylationDrug Resistance, NeoplasmTranscription FactorsAnimalsCell Line, TumorCell ProliferationCellular SenescenceDNA-Binding ProteinsDNA HelicasesGene Expression Regulation, NeoplasticHumansMiceNeoplasmsNuclear ProteinsCDKN2A protein, humanCyclin-Dependent Kinase Inhibitor p16DNA-Binding ProteinsDNA HelicasesNuclear ProteinsPolycomb Repressive Complex 2SMARCA4 protein, humanTranscription Factors

Identifiers

PMID39500892
PMCPMC11538500

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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.