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SRSF10 promotes cisplatin resistance in bladder cancer via BIN1 Exon 12 retention and ANXA1 activation

Oncogene (2026)Cite this article

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Abstract

RNA alternative splicing is a fundamental post-transcriptional mechanism that plays a key role in generating protein diversity. Previous studies from our group have shown that overexpression SRSF10 could promote liver cancer cell proliferation and invasion. However, its involvement in bladder cancer remains poorly understood. In the present study, we investigated SRSF10 expression using data from TCGA and GEO databases, immunohistochemistry, and proteomics. Functional validation was performed through in vitro and in vivo experiments, RNA sequencing, and bioinformatics analysis. Additionally, Co-Immunoprecipitation was utilized to confirm the interaction between BIN1(12+) and ANXA1. Our results demonstrate that SRSF10 is overexpressed in bladder cancer, with its expression correlating with poor prognosis and advanced clinical stages. Functional assays revealed that SRSF10 knockdown significantly decreased cell proliferation and cisplatin IC50, while its overexpression had the opposite effect. These findings were further validated in xenograft models and clinical samples. Mechanistically, we show that SRSF10 induces the retention of BIN1 exon 12, resulting in the upregulation of the BIN1(12+) isoform. BIN1(12+) directly interacts with and activates ANXA1, thereby contributing to cisplatin resistance. In conclusion, SRSF10 enhances cisplatin resistance in bladder cancer through the BIN1(12+)/ANXA1 signaling axis, suggesting its potential as a therapeutic target for bladder cancer.

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Fig. 1: SRSF10 is highly expressed in BLCA, and its high expression is negatively correlated with patient prognosis.
Fig. 2: High expression of SRSF10 is positively correlated with cisplatin resistance in BLCA.
Fig. 3: High expression of SRSF10 leads to cisplatin resistance in BLCA.
Fig. 4: BIN1(12+) Promotes Cisplatin Resistance in BLCA.
Fig. 5: BIN1(12+) directly binds to ANXA1 protein and promotes its expression.
Fig. 6: SRSF10 promotes cisplatin resistance in bladder cancer through the BIN1(12+)/ANXA1 axis.
Fig. 7

Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

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Funding

Thanks all the authors for your excellent work. This work was supported by National Natural Science Foundation of China (No. 82473260; No. 82403854), Central South University Research Programme of Advanced Interdisciplinary Studies(2023QYJC017), and the Wisdom Accumulation and Talent Cultivation Project of the Third Xiangya hospital of Central South University (BJ202001), the Natural Science Foundation of Hunan Province(2024JJ3044), the Major Scientific Research Program for High-level Talents in Healthcare of Hunan Province(R2023021), Natural Science Foundation of Hunan Province (No. 2024JJ6606), Natural Science Foundation of Changsha (No.93674), China Postdoctoral Science Foundation (No.2024M753681), Postdoctoral Fellowship Program of CPSF (GZC20233168).

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Author notes

  1. These authors contributed equally: Mengqing Xiao, Yanni Ma.

Authors and Affiliations

  1. Department of Oncology, Third Xiangya Hospital of Central South University, Changsha, 410013, China

    Mengqing Xiao, Yanni Ma, Ganghua Zhang, Guanjun Chen, Yuxing Zhu, Yaxin Cheng, Ziyang Feng & Ke Cao

  2. Department of Gastroenterology, Third Xiangya Hospital of Central South University, Changsha, 410013, China

    Xiaoming Liu

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Contributions

MQX and KC designed the study, analyzed and interpreted the data, and wrote the manuscript. GHZ, YXZ and GJC contributed to data acquisition, analysis and interpretation. MQX, GJC, and YXC carried out the experiments. XML, and ZYF provide technical expertise and support. YNM conducted the revison work. All authors have seen and approved the final version of the manuscript.

Corresponding author

Correspondence to Ke Cao.

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The authors declare no competing interests.

Ethics approval and consent to participate

The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the ethics committee of the Third Xiangya Hospital of Central South University (No. 2021-S141). All the animals received human care. Ten human bladder cancer specimens were collected from the Third Xiangya Hospital of Central South University between January 2019 and December 2023, and patient consent was waived due to the retrospective design of the study and approval from the ethics committee.

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Xiao, M., Ma, Y., Zhang, G. et al. SRSF10 promotes cisplatin resistance in bladder cancer via BIN1 Exon 12 retention and ANXA1 activation. Oncogene (2026). https://doi.org/10.1038/s41388-026-03735-7

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