Work

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

Year: 2026

Type: article

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.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1921855