Evidence map›Paper›PMID 40405208›Full record

ArticleJournal of translational medicine2025

SRSF1-mediated alternative splicing regulates bladder cancer progression and cisplatin sensitivity through HIF1A/BNIP3/mitophagy axis.

Qikai Wu, Hao Yu, Huanyou Sun, Jiancheng Lv, Juntao Zhuang, Lingkai Cai, Lingjing Jiang, Yuhan Chen, Yiran Tao, Kexin Bai and 3 more

Abstract read
In one paragraph

Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

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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.

Qikai Wu *Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Hao Yu *Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Huanyou Sun *Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Jiancheng Lv *Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Juntao ZhuangDepartment of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Lingkai CaiDepartment of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Lingjing JiangDepartment of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Yuhan ChenDepartment of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Yiran TaoDepartment of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Kexin BaiDepartment of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Haiwei YangDepartment of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. haiweiyang@njmu.edu.cn.
Xiao YangDepartment of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. yangxiao2915@163.com.
Qiang LuDepartment of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. doctorlvqiang@njmu.edu.cn.ORCID 0000-0003-3589-2507

Funding

Jiangsu Province Capability Improvement Project through Science, Technology and Education ZDXK202219Jiangsu Province Hospital (the First Affiliated Hospital of Nanjing Medical University) Clinical Capacity Enhancement Project JSPH-MA-2022-5National Natural Science Foundation of China 82072832National Natural Science Foundation of China 82073306National Natural Science Foundation of China 82273152Natural Science Foundation of Jiangsu Province BK20241128
6 · The paper itself

Abstract

backgroundAlternative splicing (AS) is consistently linked to tumor progression. SRSF1, the first identified proto-oncogene in the serine/arginine-rich splicing factor (SRSF) protein family, plays a crucial role. However, the specific functions and potential mechanisms of SRSF1 in advancing bladder cancer (BCa) progression and influencing chemosensitivity remain largely unexplored.

methodsThe expression of SRSF1 in BCa tissues and cell lines was investigated using quantitative real-time PCR (RT-qPCR) and western blotting. Survival analysis was employed to examine the association between SRSF1 expression and prognosis of BCa. The functions of SRSF1 were evaluated through proliferation assays, migration assays, IC50 determination assays, and tumorigenesis assays in nude mice. Subsequent RNA sequencing validated the relationship between SRSF1 alternative splicing and the mitophagy pathway. Mitochondrial membrane potential (MMP) was assessed using JC-1 staining. Mitophagy and autophagic flux were quantified using transmission electron microscopy and fluorescence imaging. RNA immunoprecipitation, CUT & RUN assays, and luciferase reporter assays were performed to validate the SRSF1/HIF1A/BNIP3 axis.

resultsHigh expression of SRSF1 in BCa was significantly associated with poor prognosis. SRSF1 promoted the progression of BCa cells and conferred resistance to cisplatin both in vitro and in vivo. Mechanistically, SRSF1 interacted with pre-HIF1A via the RRM1/RRM2 domain, thereby enhancing the production of the transcription factor HIF1A through the alternative splicing pathway. This interaction subsequently activated the HIF1A/BNIP3 axis, which promoted mitophagy in BCa. Ultimately, this led to further progression of bladder cancer and a decrease in cisplatin sensitivity.

conclusionsSRSF1 indicated poor prognosis and promoted the progression and cisplatin resistance of BCa cells through the HIF1A/BNIP3/mitophagy axis. It holds significant potential as a novel biomarker for the diagnosis and treatment of BCa, particularly in chemotherapy.

Indexed as

Alternative SplicingCisplatinDisease ProgressionHypoxia-Inducible Factor 1, alpha SubunitSerine-Arginine Splicing FactorsUrinary Bladder NeoplasmsAnimalsAutophagyCell Line, TumorCell MovementCell ProliferationDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticHumansMaleCisplatinHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitMAS1 protein, humanProto-Oncogene MasSerine-Arginine Splicing FactorsSRSF1 protein, humanAlternative splicingBladder cancerCisplatin resistanceMitophagySRSF1

Identifiers

PMID40405208
PMCPMC12096585

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Registered trials

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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.