Snai2-mediated upregulation of NADSYN1 promotes bladder cancer progression by interacting with PHB

Prohibitin (PHB) plays a significant role in cancer processes whereas its mechanism in bladder cancer (BC) aggressiveness is not fully understood. This study aimed to investigate the role of PHB in BC aggressiveness. The study employed a range of in vivo and in vitro assays to elucidate the interaction between PHB-NADSYN1 and its underlying function in BC progression. We found that PHB was upregulated in muscle-invasive bladder cancer tissues, and bound to NADSYN1 mRNA in BC tissues more than in adjacent normal tissues. NADSYN1 and PHB were upregulated and positively correlated both in BC tissues and cell lines. We further revealed that deleting NADSYN1 prevented PHB-mediated cell invasiveness of BC in vivo and in vitro. PHB could directly bind to NADSYN1 mRNA, and it was found that the PHB domain was responsible for the PHB-NADSYN1 interaction. Depletion of NADSYN1 expression significantly decreased the protein level of PHB. In addition, Snai2 positively correlated with NADSYN1 and depletion or mutation of Snai2 binding sites inhibited NADSYN1-PHB-mediated BC progression. The study highlights a novel Snai2-NADSYN1-PHB mechanism in BC progression and indicates that PHB and NADSYN1 could serve as a therapeutic target for BC Overall design: We initially utilized high-throughput RNAseq method to identify differential gene expressions between MIBC and NMIBC tisseus.By intersecting three different groups, we pinpointed 10 specific genes that exhibited differential expression. MIBC, muscle-invasive bladder cancer; NMIBC, non-muscle-invasive bladder cancer. We repeated the high-throughput RNAseq 3 times (2 pairs of specimens at a time) to compare the differential genes between MIBC and NMIBC, and by taking the intersection of the differential genes 3 times, we obtained 10 differential genes