Evidence mapPaperPMID 41310897Full record

ArticleHereditas2025

Integrative multi-omics and single-cell transcriptomics reveal ARHGEF12 driving chemoresistance in bladder cancer.

Kunyao Zhu, Zhejiao Zhang, Tinghao Li, Yan Sun, Junlong Zhu, Linfeng Wu, Xiaoyu Zhang, Hang Tong, Zijia Qin, Aimin Wang and 1 more

Abstract read
In one paragraph

Article in Hereditas, 2025. 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

11 authors.

Kunyao ZhuDepartment of Urology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, P.R. China.
Zhejiao ZhangDepartment of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Tinghao LiDepartment of Urology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, P.R. China.
Yan SunDepartment of Urology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, P.R. China.
Junlong ZhuDepartment of Urology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, P.R. China.
Linfeng WuDepartment of Urology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, P.R. China.
Xiaoyu ZhangDepartment of Urology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, P.R. China.
Hang TongDepartment of Urology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, P.R. China.
Zijia QinDepartment of Urology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, P.R. China.
Aimin WangDepartment of Urology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, P.R. China.
Weiyang HeDepartment of Urology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, P.R. China. weiyang1262020@126.com.

Funding

Chongqing Biomedicine Key R&D Project CSTB2021TIAD- KPX0041the National Natural Science Foundation of China No. 82372881
6 · The paper itself

Abstract

Bladder cancer (BLCA) is the predominant type of urothelial carcinoma in urinary system, and resistance to cisplatin-based chemotherapy substantially worsens clinical outcomes, presenting a major therapeutic obstacle. In this study, we integrated genome-wide association study (GWAS) data with expression quantitative trait loci (eQTL) analyses, and applied Mendelian randomization (MR) to assess the causal effects of eQTLs from 19,942 genes on BLCA. By incorporating scRNA-seq data, our study also identifies differentially expressed genes (DEGs) in cisplatin-resistant BLCA cells and examined their causal associations with BLCA, aiming to elucidate genetic drivers of chemoresistance and tumor progression. Through this integrated approach, we identified the eQTL of the ARHGEF12 gene as a key mediator of cisplatin resistance. Bioinformatic analysis revealed that elevated ARHGEF12 expression was strongly associated with activation of the PI3K/Akt signaling pathway. To define ARHGEF12's role in cisplatin resistance, we established a cisplatin-resistant UM-UC-3/DDP model. Silencing ARHGEF12 markedly reduced chemoresistance, increased apoptotic cell death, and induced pronounced morphological changes. Pharmacological modulation with the ROCK inhibitor Y-27632 and a rescue assay with the Akt activator SC79 supported a model in which ARHGEF12 drives chemoresistance via RhoA/ROCK-dependent activation of the PI3K/AKT axis. This study is the first to integrate MR with single-cell transcriptomics to explore the genetic contribution to cisplatin resistance in BLCA. Our results uncover a novel mechanistic role of ARHGEF12 in BLCA progression and chemoresistance and suggest it as a potential therapeutic target for precision treatment strategies.

Indexed as

Drug Resistance, NeoplasmRho Guanine Nucleotide Exchange FactorsTranscriptomeUrinary Bladder NeoplasmsAntineoplastic AgentsCell Line, TumorCisplatinGene Expression Regulation, NeoplasticGenome-Wide Association StudyHumansMultiomicsQuantitative Trait LociSignal TransductionSingle-Cell AnalysisAntineoplastic AgentsCisplatinRho Guanine Nucleotide Exchange FactorsARHGEF12Bladder cancerChemoresistanteQTLsMendelian randomization

Identifiers

PMID41310897
PMCPMC12661753

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.