Exosomal circ50547 as a potential marker and promotor of gastric cancer progression via miR-217/HNF1B axis

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Exosomes facilitate intercellular communication and tumor progression via their molecular cargo.
• Circular RNAs (circRNAs) within exosomes are implicated in various cancers.
• Gastric cancer (GC) diagnosis and progression require novel biomarkers.

Purpose of the Study:

• Investigate the role of exosomal circRNAs in gastric cancer (GC) diagnosis and progression.
• Identify and characterize a novel GC-associated exosomal circRNA.
• Elucidate the underlying molecular mechanisms of its oncogenic function.

Main Methods:

• Serum exosome characterization (TEM, NTA, Western blot).
• Functional assays (CCK-8, colony formation, Transwell, sphere formation) to assess circ50547's role in GC cell proliferation, migration, invasion, stemness, and drug resistance.
• qRT-PCR and fluorescence in situ hybridization for circ50547 expression and localization.
• Bioinformatic analysis, luciferase assays, and Western blot to determine molecular mechanisms.

Main Results:

• A novel GC-derived exosomal circRNA, hsa_circ_0050547 (circ50547), was identified.
• Circ50547 exhibited significantly higher expression in GC tissues and serum exosomes compared to controls.
• Exosomal circ50547 demonstrated superior diagnostic value over serum circ50547.
• Circ50547 overexpression promoted GC cell proliferation, migration, invasion, stemness, and drug resistance, while knockdown had opposite effects.
• Mechanistically, circ50547 functions as a sponge for miR-217, regulating HNF1B expression and promoting GC progression.

Conclusions:

• Exosomal circ50547 is a potential diagnostic and prognostic biomarker for gastric cancer (GC).
• Circ50547 exhibits oncogenic properties in GC.
• The oncogenic role of circ50547 is mediated through the miR-217/HNF1B signaling pathway in GC.