The FOXM1/RNF26/p57 axis regulates the cell cycle to promote the aggressiveness of bladder cancer

• Published in: Cell death & disease 2021-10, Vol.12 (10), p.944-944, Article 944
• Main Authors: Yi, Lu, Wang, Haohui, Li, Wei, Ye, Kun, Xiong, Wei, Yu, Haixin, Jin, Xin
• Format: Article
• Language: English
• Subjects: 13/105; 13/109; 13/31; 13/51; 13/89; 14; 14/1; 14/63; 631/67/395; 631/67/589/1336; Antibodies; Biochemistry; Bioinformatics; Biomedical and Life Sciences; Bladder cancer; Cancer; Cell Biology; Cell Culture; Cell Cycle; Cell Line, Tumor; Cell Proliferation - genetics; Cyclin-Dependent Kinase Inhibitor p57 - metabolism; Disease Progression; Forkhead Box Protein M1 - metabolism; Gene Expression Regulation, Neoplastic; Humans; Immunology; Life Sciences; Models, Biological; Neoplasm Invasiveness; Neoplasm Proteins - metabolism; Prognosis; Protein Binding; Risk factors; Signal Transduction; Transcription; Up-Regulation; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - pathology
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-021-04260-z

Bladder cancer is one of the most lethal cancers in the world. Despite the continuous development of medical technologies and therapeutic strategies, the overall survival rate of bladder cancer has not changed significantly. Targeted therapy is a new promising method for bladder cancer treatment. Thus, an in-depth study of the molecular mechanism of the occurrence and development of bladder cancer is urgently needed to identify novel therapeutic candidates for bladder cancer. Here, bioinformatics analysis demonstrated that RNF26 was one of the risk factors for bladder cancer. Then, we showed that RNF26 is abnormally upregulated in bladder cancer cells and tissues and that higher RNF26 expression is an unfavorable prognostic factor for bladder cancer. Moreover, we found that RNF26 promotes bladder cancer progression. In addition, we showed that RNF26 expression is promoted by FOXM1 at the transcriptional level through MuvB complex. The upregulated RNF26 in turn degrades p57 (CDKN1C) to regulate the cell cycle process. Collectively, we uncovered a novel FOXM1/RNF26/p57 axis that modulates the cell cycle process and enhances the progression of bladder cancer. Thus, the FOXM1/RNF26/p57 signaling axis could be a candidate target for the treatment of bladder cancer.