Circular RNA circ_SKA3 enhances gastric cancer development by targeting miR-520h

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Gastric cancer (GC) remains a significant global health challenge with complex underlying molecular mechanisms.
• Circular RNAs (circRNAs) are emerging as critical regulators in various cancers, including GC, but their specific roles are often not fully elucidated.

Purpose of the Study:

• To investigate the functional role and molecular mechanisms of circ_SKA3 in the progression of gastric cancer.
• To elucidate the interaction between circ_SKA3, microRNA-520h (miR-520h), and cell division cycle 42 (CDC42) in GC.

Main Methods:

• Quantitative real-time PCR (qRT-PCR) and Western blot were used to measure the expression levels of circ_SKA3, miR-520h, and CDC42.
• Functional assays including MTT, EdU, colony formation, flow cytometry, and transwell assays were performed to assess cell proliferation, apoptosis, cell cycle, migration, and invasion.
• Dual-luciferase reporter assays and *in vivo* mouse xenograft models were employed to validate molecular interactions and oncogenic effects.

Main Results:

• Circ_SKA3 was found to be overexpressed in GC tissues and cells, correlating with tumor progression.
• Downregulation of circ_SKA3 significantly inhibited GC cell proliferation, colony formation, migration, and invasion, while promoting apoptosis *in vitro* and suppressing tumor growth *in vivo*.
• Circ_SKA3 was shown to directly bind to miR-520h, regulating CDC42 expression via this interaction, thereby influencing GC cell behaviors.

Conclusions:

• The study establishes the miR-520h/CDC42 axis as a key molecular mechanism through which circ_SKA3 exerts its oncogenic role in gastric cancer.
• Circ_SKA3 acts as a molecular sponge for miR-520h, leading to increased CDC42 expression and promoting GC progression.
• Targeting the circ_SKA3/miR-520h/CDC42 pathway presents a potential therapeutic strategy for gastric cancer treatment.