Liang Jiaming, Guo Shuyue, Wang Youzhi, Cao Qian, Guo Tao, Zhou Diansheng, Li Junbo, Liao Yihao, Zhong Boqiang, Jiang Ning
Tianjin institute of Urology, The Second Hospital of Tianjin Medical University, 23 Pingjiang Road, Hexi District, Tianjin, 300211, China.
Department of Diagnostic and Therapeutic Ultrasonography, Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, National Clinical Research Center of Cancer, Tianjin, China.
Cancer Cell Int. 2025 Jun 17;25(1):214. doi: 10.1186/s12935-025-03851-6.
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.
LINC00525是一种长链非编码RNA（lncRNA），已被证明参与多种类型癌症进展的调控。然而，其在膀胱癌（BLCA）中的作用仍未得到证实。在本研究中，我们观察到与正常对照相比，膀胱癌组织和细胞系中LINC00525的表达均上调。在收集的12对组织样本中，LINC00525在肌层浸润性膀胱癌（MIBC）组织中的表达水平高于非肌层浸润性膀胱癌（NMIBC）组织，表明LINC00525水平与膀胱癌进展呈正相关。体外实验表明，敲低LINC00525可显著抑制膀胱癌细胞系的增殖、迁移和侵袭；相反，LINC00525的过表达则产生相反的效果。生物信息学分析揭示了LINC00525与YAP之间的关联，这通过使用患者组织进行的蛋白质免疫印迹和PCR分析得到进一步证实。机制上，我们发现LINC00525降低了YAP丝氨酸127（S127）位点的磷酸化，促进其核内转运，从而对靶基因发挥转录调控作用。此外，LINC00525通过作用于YAP赖氨酸321（K321）抑制YAP泛素化，从而增加其稳定性以防止降解。通过体内和体外实验，我们证明了LINC00525通过YAP介导对膀胱癌细胞和肿瘤生长具有促进作用。我们的研究揭示了LINC00525/YAP轴参与调控膀胱癌的发生发展，为以LINC00525高表达为特征的恶性肿瘤提供了潜在的治疗策略。
