LINC00525 drives aggressive phenotypes in bladder cancer via YAP stabilization-mediated transcriptional activation.

Abstract

LINC00525, a long noncoding RNA (lncRNA), has been implicated in the regulation of cancer progression across various types. However, its role in bladder cancer (BLCA) remains unconfirmed. In this study, we observed upregulation of LINC00525 expression in both bladder cancer tissues and cell lines compared to normal controls. Among the 12 pairs of collected tissue samples, LINC00525 exhibited higher expression levels in muscle-invasive bladder cancer (MIBC) tissues than in non-muscle-invasive bladder cancer (NMIBC) tissues, indicating a positive correlation between LINC00525 levels and bladder cancer progression. In vitro experiments demonstrated that knockdown of LINC00525 significantly inhibited proliferation, migration, and invasion of bladder cancer cell lines; conversely, overexpression of LINC00525 had the opposite effect. Bioinformatic analysis revealed an association between LINC00525 and YAP, which was further confirmed by western blotting and PCR analysis using patient tissues. Mechanistically, we found that LINC00525 reduced phosphorylation of YAP at serine 127 (S127), promoting its nuclear import to exert transcriptional regulatory effects on target genes. Additionally, LINC00525 inhibited YAP ubiquitination by acting on YAP lysine 321 (K321), thereby increasing its stability to prevent degradation. Through in vivo and in vitro experiments, we demonstrated the YAP-mediated promoting effect of LINC00525 on bladder cancer cells and tumor growth. Our study reveals the involvement of the LINC00525/YAP axis in regulating bladder cancer development, suggesting a potential therapeutic strategy for malignant tumors characterized by high levels of LINC00525 expression.