Evidence map›Paper›PMID 40971821›Full record

ArticleNeuro-oncology2026

Co-activation of the super-enhancer complex SOX2 and HDAC1 confers temozolomide resistance by promoting PDGFB transcription in glioblastoma.

Han Xie, Tongjie Ji, Chunyu Zhang, Meng Cheng, Rui Wang, Yueyao Wu, Jingzhe Wang, Honghao Wang, Junyu Yang, Siyi Xu and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 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

13 authors.

Han XieDepartment of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China (H.X., T.J., C.Z., M.C., R.W., Y.W., J.W., H.W., J.Y., S.X., M.L., J.Z., C.Z.).
Tongjie JiDepartment of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China (H.X., T.J., C.Z., M.C., R.W., Y.W., J.W., H.W., J.Y., S.X., M.L., J.Z., C.Z.).
Chunyu ZhangDepartment of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China (H.X., T.J., C.Z., M.C., R.W., Y.W., J.W., H.W., J.Y., S.X., M.L., J.Z., C.Z.).
Meng ChengDepartment of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China (H.X., T.J., C.Z., M.C., R.W., Y.W., J.W., H.W., J.Y., S.X., M.L., J.Z., C.Z.).
Rui WangInstitute for Advanced Study, Tongji University, Shanghai, 20092, China (J.Z.).
Yueyao WuInstitute for Advanced Study, Tongji University, Shanghai, 20092, China (J.Z.).
Jingzhe WangInstitute for Advanced Study, Tongji University, Shanghai, 20092, China (J.Z.).
Honghao WangInstitute for Advanced Study, Tongji University, Shanghai, 20092, China (J.Z.).
Junyu YangDepartment of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China (H.X., T.J., C.Z., M.C., R.W., Y.W., J.W., H.W., J.Y., S.X., M.L., J.Z., C.Z.).
Siyi XuDepartment of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China (H.X., T.J., C.Z., M.C., R.W., Y.W., J.W., H.W., J.Y., S.X., M.L., J.Z., C.Z.).
Min LiuDepartment of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China (H.X., T.J., C.Z., M.C., R.W., Y.W., J.W., H.W., J.Y., S.X., M.L., J.Z., C.Z.).
Jing ZhangDepartment of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China (H.X., T.J., C.Z., M.C., R.W., Y.W., J.W., H.W., J.Y., S.X., M.L., J.Z., C.Z.).ORCID 0000-0003-3155-6768
Chunlong ZhongDepartment of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China (H.X., T.J., C.Z., M.C., R.W., Y.W., J.W., H.W., J.Y., S.X., M.L., J.Z., C.Z.).ORCID 0000-0002-0605-7273

Funding

Clinical Research Special Funding of the Shanghai Municipal Health Commission 202340112Key Discipline Construction Project of Shanghai East Hospital 2024-DFZD-003SKey Disciplines Group Construction Project of Shanghai Pudong New Area Health Commission PWZxq2022-10National Natural Science Foundation of China 82172820Natural Science Foundation of Shanghai 22ZR1466200Research Funds for the Central Universities 22120240228Research Funds for the Central Universities 22120250457
6 · The paper itself

Abstract

backgroundTemozolomide (TMZ) resistance remains the major obstacle in the treatment of glioblastoma (GBM). We previously found that the super-enhancer (SE) complex is involved in the regulation of genes related to tumor biology, but its mechanisms in mediating TMZ resistance in GBM remain poorly characterized.

methodsComprehensive in vitro and in vivo functional experiments were conducted using patient-derived cells (PDCs), patient-derived organoids, and PDCs xenograft models. Cleavage Under Targets and Tagmentation, chromatin immunoprecipitation, co-immunoprecipitation, mass spectrometry, protein fragment complementation assay, dual-luciferase reporter assay, fluorescence polarization assay, and surface plasmon resonance assay were employed to unravel the molecular mechanisms.

resultsWe found that SOX2 is significantly upregulated in TMZ-resistant PDCs and associated with the poor prognosis of recurrent GBM patients. Moreover, inhibition of SOX2 enhanced TMZ-induced apoptosis and DNA damage response, thereby promoting TMZ chemosensitivity. Mechanically, we identified PDGFB as a novel SE-associated oncogene mediated by SOX2. SE complex SOX2 and HDAC1 were recruited together to the SE region of PDGFB, synergistically triggering the PDGFB-MAPK/PI3K signaling axis and ultimately promoting TMZ resistance. Notably, virtual screening targeting the critical interaction domain between SOX2 and HDAC1 identified the FDA-approved drug fluvastatin as a potent SOX2 inhibitor that effectively sensitizes GBM cells to TMZ.

conclusionsTargeting the SE complex enhances TMZ chemosensitivity in GBM, providing a promising therapeutic avenue to overcome drug resistance and improve clinical outcomes.

Indexed as

Brain NeoplasmsDrug Resistance, NeoplasmGlioblastomaHistone Deacetylase 1SOXB1 Transcription FactorsTemozolomideAnimalsAntineoplastic Agents, AlkylatingApoptosisCell ProliferationGene Expression Regulation, NeoplasticHumansMiceMice, NudePrognosisTumor Cells, CulturedAntineoplastic Agents, AlkylatingHDAC1 protein, humanHistone Deacetylase 1SOX2 protein, humanSOXB1 Transcription FactorsTemozolomideglioblastomaPDGFBSOX2super-enhancer complextemozolomide resistance

Identifiers

PMID40971821
PMCPMC12962635

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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.