Adeno-associated virus-delivered alpha synuclein inhibits bladder cancer growth via the p53/p21 signaling pathway

Alpha-synuclein (alpha-syn), encoded by the SNCA gene, is a major participant in the pathophysiology of Parkinson's disease (PD). Its functions have been reported to be related to apoptosis induction, the elevation of oxidative stress, mitochondrial homeostasis, cell-cycle aberrations, and DNA-related interactions. Evidence obtained in recent studies suggests a possible link between alpha-syn and cancer development. Bladder cancer (BCa) is the second most common genitourinary malignancy, with the population of survivors of BCa increasing worldwide. In this study, we show that alpha-syn expression was significantly downregulated in BCa. In vitro and in vivo experiments showed that alpha-syn could significantly inhibit BCa cell proliferation by arresting the cell cycle in the S phase via upregulation of p53 expression mediated by DNA damages. Further experiments showed that overexpression of alpha-syn delivered by adeno-associated viruses (AAVs) exerted inhibitory effects on the growth of BCa tumors. These findings indicate that alpha alpha-syn is a functional tumor suppressor that can inhibit the proliferation of BCa cells by activating the p53/p21 signaling pathway. Our present study provides insights into the roles of alpha-syn in BCa and suggests that alpha-syn may be a novel therapeutic target for the treatment of BCa.

Automated summary

This study reveals that alpha-synuclein is significantly downregulated in bladder cancer and can inhibit the proliferation of bladder cancer cells through activation of the p53/p21 signaling pathway. These findings provide insights into the potential application of alpha-synuclein in the treatment of bladder cancer.