Alpha-2 Heremans Schmid Glycoprotein (AHSG) promotes the proliferation of bladder cancer cells by regulating the TGF-β signalling pathway

Abstract

ABSTRACT Bladder cancer (BC) is one of the most common urinary tract malignancies and is the tenth most common cancer globally. Alpha-2 Heremans Schmid Glycoprotein (AHSG) is a multifunctional protein that plays different roles in the progression of multiple tumors. However, the role and mechanism of AHSG in the development and progression of BC are unknown. AHSG expression was assessed in BC cells and tissues using western blot and immunohistochemistry. Using plasmid and siRNA, overexpressed and knocked down AHSG in BC cells were constructed. A series of functional experiments, including CCK8, plate clone formation, and flow cytometry, were performed to evaluate cell proliferation and cycle. AHSG was expressed higher in BC cells and tissues than in normal bladder epithelial cells and non-tumor tissues. Functionally, the overexpression of AHSG significantly increased the proliferation of BC cells and promoted the cell cycle from G1 to the S phase, whereas the knockdown of AHSG gave the opposite result.Additionally, western blot results revealed that AHSG expression level was negatively correlated with the phosphorylation level of Smad2/3 protein, a key downstream molecule of the traditional TGF-β signaling pathway, suggesting that AHSG could antagonize the traditional TGF-β signaling pathway. Finally, the expression level of AHSG in the urine of BC patients was significantly higher than that of healthy subjects by ELISA, with specificity. Our study concluded that AHSG might be a novel marker of BC that promotes the proliferation of BC cells by regulating the TGF-β signaling pathway.