Inhibitory effects of circR-127aa on gastric cancer progression and tumor growth

This study investigates the function of a newly identified 127-amino acid peptide, circR-127aa, encoded by hsa_circ_0075402 (circRACK1), in gastric cancer (GC), a condition with significant prevalence in China. Utilizing a comprehensive analysis of circular RNA (circRNA) ribosome profiling data alongside experimental validations through mass spectrometry, Western blot, and immunofluorescence, we demonstrate that circR-127aa Inhibits Malignant Phenotypes and suppresses tumor growth in nude mice models. Significantly, the interaction of circR-127aa with Vimentin, a crucial element in actin-actin-cytoskeletal remodeling, indicates that circR-127aa functions as a tumor suppressor by facilitating the ubiquitination of Vimentin. These findings advance our comprehension of gastric cancer (GC) progression and propose circR-127aa as a promising therapeutic target and biomarker in the management of GC. •circR-127aa Discovery: Identifies circR-127aa, a peptide from circular RNA circRACK1, acting as a gastric cancer tumor suppressor by binding to Vimentin.•Tumor Suppression Mechanism: Shows circR-127aa promotes Vimentin degradation, reducing cell proliferation and invasion in gastric cancer.•Cancer Cell Dynamics: Reveals circR-127aa inhibits EMT, affecting cell motility and invasiveness, by regulating EMT markers.•Therapeutic Potential: Confirms circR-127aa's role in reducing tumor growth and metastasis in nude mice, suggesting its use as a gastric cancer therapeutic.•Clinical Relevance: Proposes circR-127aa as a biomarker and therapeutic target, enhancing gastric cancer detection and treatment strategies.