RBPMS inhibits bladder cancer metastasis by downregulating MYC pathway through alternative splicing of ANKRD10

Area of Science:

• Molecular Biology
• Cancer Research
• Genetics

Background:

• Alternative splicing (AS) is crucial in gene regulation and is often dysregulated in cancer.
• RNA-binding proteins (RBPs) orchestrate AS, making them key players in disease pathogenesis.
• Bladder cancer (BLCA) exhibits significant AS dysregulation, impacting patient prognosis.

Purpose of the Study:

• To identify RBPs involved in BLCA and elucidate their functional roles.
• To investigate the mechanism by which RBPMS influences BLCA progression.
• To explore RBPMS as a potential therapeutic target for bladder cancer.

Main Methods:

• Comprehensive screening of the TCGA-BLCA cohort to identify differentially expressed RBPs.
• Functional assays to assess the impact of RBPMS on BLCA cell migration and epithelial-mesenchymal transition (EMT).
• RNA-sequencing (RNA-Seq) to identify target mRNAs regulated by RBPMS, including ANKRD10, and subsequent mechanistic studies involving AS and MYC pathway activation.

Main Results:

• RBPMS was identified as a consistently downregulated RBP in BLCA, correlating with poor prognosis.
• RBPMS suppressed BLCA cell migration and EMT.
• RBPMS regulates ANKRD10 alternative splicing, leading to increased ANKRD10-2 expression, which activates MYC proteins and promotes cell migration.

Conclusions:

• RBPMS acts as a tumor suppressor in BLCA by inhibiting cell migration and invasion.
• The RBPMS-ANKRD10-MYC axis represents a novel regulatory pathway in bladder cancer.
• Targeting this pathway holds promise for developing new therapeutic strategies for BLCA.