CircPGM5 regulates Foxo3a phosphorylation via MiR-21-5p/MAPK10 axis to inhibit bladder cancer progression

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Bladder cancer (BC) is a prevalent malignancy, particularly in males.
• Circular RNAs (circRNAs) play a role in BC progression, but their mechanisms require further study.
• Identifying novel circRNAs and their functions is crucial for understanding BC pathogenesis.

Purpose of the Study:

• To identify and characterize a novel circRNA, circPGM5, in bladder cancer.
• To investigate the functional role and underlying mechanism of circPGM5 in BC.
• To explore circPGM5 as a potential therapeutic target for BC.

Main Methods:

• High-throughput sequencing to screen for novel circRNAs.
• Quantitative real-time PCR (qRT-PCR) to assess circPGM5 expression levels in BC tissues and cell lines.
• RNA fluorescence in situ hybridization (FISH) to determine subcellular localization.
• In vitro assays (proliferation, migration, invasion) and in vivo tumor models to evaluate functional effects.
• Mechanistic studies involving microRNA (miRNA) interaction and downstream signaling pathway analysis.

Main Results:

• circPGM5 was found to be significantly downregulated in BC tissues and cell lines.
• Lower circPGM5 expression correlated with advanced stage, grade, and lymphatic metastasis in BC patients.
• Overexpression of circPGM5 suppressed BC cell proliferation, migration, and invasion in vitro and inhibited tumor growth and metastasis in vivo.
• Mechanistically, circPGM5 acts as a sponge for miR-21-5p, upregulating MAPK10 expression and subsequently affecting Foxo3a phosphorylation.

Conclusions:

• circPGM5 functions as a tumor suppressor in bladder cancer.
• The circPGM5/miR-21-5p/MAPK10/Foxo3a axis represents a novel regulatory pathway in BC.
• circPGM5 holds potential as a diagnostic biomarker and therapeutic target for bladder cancer.