Evidence map›Paper›PMID 41872171›Full record

ArticleNature communications2026

RFC4 drives temozolomide resistance in glioblastoma by activating STK38-BECN1-dependent autophagy.

Min Mao, Hang Ji, Wen-Qian Yu, Qu-Jing Gai, Qiang Sun, Qian Yan, Sen-Lin Xu, Meng-Li Zhu, Mei-Hua Qu, Han-Min Liu and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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

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

14 authors.

Min MaoThe Joint Laboratory for Lung Development and Related Diseases of West China Second University Hospital, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, PR China.
Hang JiDepartment of Neurosurgery, West China Hospital, Sichuan University, Chengdu, PR China.
Wen-Qian YuDepartment of Epidemiology and Biostatistics, West China School of Public Health, West China Fourth Hospital, Sichuan University, Chengdu, PR China.
Qu-Jing GaiInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, PR China.
Qiang SunInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, PR China.
Qian YanInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, PR China.
Sen-Lin XuInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, PR China.
Meng-Li ZhuChongqing Advanced Pathology Research Institute, Jinfeng Laboratory, Chongqing, PR China.
Mei-Hua QuTranslational Medical Center, Department of Pulmonary and Critical Care Medicine, Weifang Second People's Hospital, Weifang, PR China.ORCID http://orcid.org/0000-0003-2464-6773
Han-Min LiuThe Joint Laboratory for Lung Development and Related Diseases of West China Second University Hospital, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, PR China.ORCID http://orcid.org/0000-0002-4633-911X
Jean-Philipe HugnotChongqing Advanced Pathology Research Institute, Jinfeng Laboratory, Chongqing, PR China.
Xi HeShapingba Hospital affiliated to Chongqing University, Chongqing, PR China. 364801909@qq.com.
Xin WangDepartment of Epidemiology and Biostatistics, West China School of Public Health, West China Fourth Hospital, Sichuan University, Chengdu, PR China. wangxinmarine@126.com.ORCID http://orcid.org/0000-0001-9325-3194
Yan WangInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, PR China. ywang@tmmu.edu.cn.ORCID http://orcid.org/0000-0002-8150-5486

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glioblastoma (GBM) remains a lethal brain tumor due to therapy resistance. While autophagy contributes to temozolomide (TMZ) resistance, its regulation is incompletely understood. This study investigates the role of replication factor RFC4, which is associated with poor prognosis and TMZ resistance in GBM. Multi-omics analyses and molecular experiments reveal that TMZ-induced chromatin accessibility enables transcription factor YY1 to bind the RFC4 promoter and upregulate its expression. RFC4, in turn, stabilizes the kinase STK38, which is essential for autophagosome formation. The RFC4-STK38 interaction facilitates BECN1 recruitment, thereby activating autophagy. Phosphorylation of STK38 at T444 stabilizes this complex, whereas a phospho-deficient mutant impairs autophagy. In vivo, RFC4 overexpression confers TMZ resistance, reversible by autophagy inhibition. Thus, our findings identify the RFC4-STK38-BECN1 axis as a mechanism underlying TMZ resistance and a potential target for precision therapy in GBM.

Indexed as

AutophagyBeclin-1Brain NeoplasmsDrug Resistance, NeoplasmGlioblastomaProtein Serine-Threonine KinasesReplication Protein CTemozolomideAnimalsAntineoplastic Agents, AlkylatingCell Line, TumorGene Expression Regulation, NeoplasticHumansMicePhosphorylationAntineoplastic Agents, AlkylatingBeclin-1BECN1 protein, humanProtein Serine-Threonine KinasesReplication Protein CTemozolomide

Identifiers

PMID41872171
PMCPMC13172434

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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 Socratic graph.