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Peer-reviewedCC BY 4.0Frontiers in Immunology

Overexpression of TUBA1A suppresses bladder cancer progression with potential modulation of autophagic activity and macrophage polarization

  • Ding-ming Song1,2
  • Hong Lu3
  • Yi-chang Shu1
  • Jia-ju Xu1
  • Yi-bo He4
  • He Duan2
  • Yan-yang Jin2
  • Shi-liang Chen4
  • Shi-chao Duan5
  • Guan-hua Jing6
  • Jia-ming Wen1
  • Ming Tong2
6 affiliations
  1. 1Department of Urology, Zhejiang University, The Second Affiliated Hospital of Zhejiang University
  2. 2Department of Urology, Jinzhou Medical University, The First Affiliated Hospital of Jinzhou Medical University
  3. 3Department of Congenital Heart Disease, General Hospital of Northern Theater Command, Postgraduate Training Base of Jinzhou Medical University
  4. 4Department of Clinical Lab, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)
  5. 5Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital
  6. 6Department of Urology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital
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Abstract

Background: Bladder urothelial carcinoma (BUC) exhibits high recurrence and poor prognosis, with limited efficacy of current immunotherapies. The role of the aggrephagy-related gene TUBA1A in the BUC immune microenvironment remains unclear.

Methods: Single-cell transcriptomic data from public repositories were analyzed to characterize the immune microenvironment. Non-negative matrix factorization identified aggrephagy-related immune–stromal subtypes, and CellChat mapped intercellular interactions. TIDE validation and KEGG enrichment defined functional modules. TUBA1A expression and function were evaluated through qRT-PCR, Western blot, proliferation, migration, apoptosis assays, and transmission electron microscopy. THP-1-derived macrophages were treated with conditioned medium from control or TUBA1A-overexpressing bladder cancer cells in the presence or absence of the autophagy inhibitor chloroquine (CQ), and polarization markers were assessed by flow cytometry and qRT-PCR. In vivo xenograft models verified tumor growth effects.

Results: Single-cell analysis identified a TUBA1A-high macrophage subset with strong immune communication and immune activity. TUBA1A was significantly downregulated in BUC tissues and cell lines. TUBA1A overexpression inhibited proliferation, migration, and invasion, promoted apoptosis, and enhanced autophagic activity (increased LC3-II and ATG5, reduced SQSTM1/p62, and elevated autophagic vesicles). Conditioned medium from TUBA1A-overexpressing cells promoted M1-like polarization; CQ abolished the induction of the M1 markers IL-12 and CD86. In vivo , TUBA1A overexpression significantly suppressed xenograft tumor growth and reduced Ki-67 expression.

Conclusion: TUBA1A is downregulated in BUC and acts as a candidate regulator of autophagic activity and macrophage polarization. TUBA1A overexpression is associated with inhibition of BUC progression, and its promotion of M1-like macrophage polarization appears to require autophagic activity. TUBA1A may represent a promising biomarker and therapeutic target for BUC.

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Cite

BibTeXRIS
BibTeX
@article{song2026overexpression,
  title = {{Overexpression of TUBA1A suppresses bladder cancer progression with potential modulation of autophagic activity and macrophage polarization}},
  author = {Ding-ming Song and Hong Lu and Yi-chang Shu and Jia-ju Xu and Yi-bo He and He Duan and Yan-yang Jin and Shi-liang Chen and Shi-chao Duan and Guan-hua Jing and Jia-ming Wen and Ming Tong},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1921855},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1921855/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Overexpression of TUBA1A suppresses bladder cancer progression with potential modulation of autophagic activity and macrophage polarization
AU  - Ding-ming Song
AU  - Hong Lu
AU  - Yi-chang Shu
AU  - Jia-ju Xu
AU  - Yi-bo He
AU  - He Duan
AU  - Yan-yang Jin
AU  - Shi-liang Chen
AU  - Shi-chao Duan
AU  - Guan-hua Jing
AU  - Jia-ming Wen
AU  - Ming Tong
PY  - 2026
DA  - 2026/10/21
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1921855
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1921855/full
AB  - Background: Bladder urothelial carcinoma (BUC) exhibits high recurrence and poor prognosis, with limited efficacy of current immunotherapies. The role of the aggrephagy-related gene TUBA1A in the BUC immune microenvironment remains unclear.  Methods: Single-cell transcriptomic data from public repositories were analyzed to characterize the immune microenvironment. Non-negative matrix factorization identified aggrephagy-related immune–stromal subtypes, and CellChat mapped intercellular interactions. TIDE validation and KEGG enrichment defined functional modules. TUBA1A expression and function were evaluated through qRT-PCR, Western blot, proliferation, migration, apoptosis assays, and transmission electron microscopy. THP-1-derived macrophages were treated with conditioned medium from control or TUBA1A-overexpressing bladder cancer cells in the presence or absence of the autophagy inhibitor chloroquine (CQ), and polarization markers were assessed by flow cytometry and qRT-PCR. In vivo xenograft models verified tumor growth effects.  Results: Single-cell analysis identified a TUBA1A-high macrophage subset with strong immune communication and immune activity. TUBA1A was significantly downregulated in BUC tissues and cell lines. TUBA1A overexpression inhibited proliferation, migration, and invasion, promoted apoptosis, and enhanced autophagic activity (increased LC3-II and ATG5, reduced SQSTM1/p62, and elevated autophagic vesicles). Conditioned medium from TUBA1A-overexpressing cells promoted M1-like polarization; CQ abolished the induction of the M1 markers IL-12 and CD86. In vivo , TUBA1A overexpression significantly suppressed xenograft tumor growth and reduced Ki-67 expression.  Conclusion: TUBA1A is downregulated in BUC and acts as a candidate regulator of autophagic activity and macrophage polarization. TUBA1A overexpression is associated with inhibition of BUC progression, and its promotion of M1-like macrophage polarization appears to require autophagic activity. TUBA1A may represent a promising biomarker and therapeutic target for BUC.
SN  - 1664-3224
ER  -