TUBA1C is a potential new prognostic biomarker and promotes bladder urothelial carcinoma progression by regulating the cell cycle

Abstract

BackgroundTUBA1C is an α-tubulin isoform involved in mitosis, and its dysregulation has been implicated in tumor progression. There is still no clear understanding of its role in bladder urothelial carcinoma (BLCA).MethodsThis study examined the differential expression of TUBA1C and its prognostic significance in bladder cancer based on data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) and also assessed the correlation of TUBA1C expression level with immune cell infiltration and immune checkpoint gene expression levels and the half-inhibitory concentration (IC50) of different chemotherapeutic agents. Immunotherapy response was estimated using the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. We detected TUBA1C expression in BLCA cells using PCR and Western blotting. Functional assays, including CCK-8, colony formation, transwell, apoptosis and cell cycle assays, were also performed to assess the oncogenic role of TUBA1C in BLCA.ResultIn three independent public cohorts, TUBA1C was significantly upregulated in bladder tumor tissues, and high TUBA1C expression in bladder cancer was associated with a poorer outcome than low expression. TUBA1C was an independent prognostic risk factor for bladder cancer, and numerous immune checkpoint genes and infiltrating immune cells were associated with TUBA1C. TIDE analysis revealed that TUBA1C showed great potential for predicting the immunotherapy response in bladder cancer patients. In addition, drug sensitivity analysis revealed that high TUBA1C expression indicated sensitivity to multiple chemotherapeutic agents. Functional assays revealed that silencing TUBA1C significantly inhibited the proliferation, migration and invasion of BLCA cells and induced apoptosis and cell cycle arrest.ConclusionThe overexpression of TUBA1C in bladder cancer predicts a poor prognosis and may also be a potential immunotherapeutic target. As a prognostic marker, TUBA1C influences tumor progression by regulating the cell cycle.