Circular RNA circLAMA3 inhibits the proliferation of bladder cancer by directly binding an mRNA

Abstract

The circular RNA (circRNA) circLAMA3 is significantly downregulated in bladder cancer tissues and cell lines. However, its function in bladder cancer has not yet been explored, and further research is needed. In this study, functional experiments demonstrated that circLAMA3 significantly inhibited the proliferation, migration, and invasion of bladder cancer cells and inhibited bladder cancer growth in vivo. Mechanistically, circLAMA3 directly binds to and promotes the degradation of MYCN mRNA, thereby reducing the MYCN protein expression in bladder cancer cells. Decreased expression of the MYCN protein inhibits the promoter activity and expression of CDK6. Ultimately, circLAMA3 affects DNA replication by downregulating CDK6, resulting in G0/G1 phase arrest and inhibition of bladder cancer proliferation. In summary, we report a potential novel regulatory mechanism via which a circRNA directly binds an mRNA and thereby regulates its fate. Moreover, circLAMA3 significantly affects the progression of bladder cancer and has potential as a diagnostic biomarker and therapeutic target for bladder cancer.

Keywords

• bladder cancer
• circLAMA3
• proliferation
• MYCN
• CDK6
• mRNA degradation