Background
Bladder cancer is a common malignancy characterized by a high recurrence rate and the development of drug resistance. Frequent mutations and gene expression alterations in the PI3K/AKT and mitogen-activated protein kinase-ERK pathways lead to deregulated cell growth and the acquisition of invasive properties, which facilitates tumour progression and confers resistance to chemotherapy. Therefore, identification of the underlying mechanisms that trigger the activation of these signalling pathways and control the invasive phenotype of tumour cells is of urgent need.
Conclusions
Overall, the results of our study suggested that alpha-crystallin B may function as a tumour-suppressive factor in bladder cancer.
Methods
We utilized publicly available gene expression databases (GEO and TCGA) and bioinformatics analysis to identify key gene expression changes in human bladder cancer . The key gene expression was detected using BC tissue microarrays. Cell proliferation, apoptosis, migration, invasion and related signalling pathways were analysed flowing transfection with key gene overexpression plasmids.
Results
The analysis revealed that inhibited expression of the alpha-crystallin B chain was a common feature in all analysed datasets. The decrease in alpha-crystallin B expression was further confirmed at the protein level using BC tissue microarrays. Overexpression of alpha-crystallin B in T24 and J82 BC cell lines resulted in significant inhibition of tumour cell migration and invasion, which was associated with a decrease in PI3K, AKT and ERK activation. Moreover, alpha-crystallin B overexpression increased the expression of E-cadherin, while reducing the expression of N-cadherin, which indicated suppression of the epithelial-mesenchymal transition. Conclusions: Overall, the results of our study suggested that alpha-crystallin B may function as a tumour-suppressive factor in bladder cancer.