A novel polypeptide encoded by the circRACK1 suppresses gastric cancer via cytoskeleton remodeling

Gastric cancer (GC), particularly prevalent in China, is associated with high rates of morbidity and mortality. This study focuses on the role and mechanistic pathways of a novel 127-amino acid peptide, circR-127aa, encoded by hsa_circ_0075402 (circRACK1) in GC cells, exploring its implications in cancer development. Circular RNAs (circRNAs), which vary in expression across different cancers, contribute to tumorigenesis via mechanisms such as miRNA sponging, protein binding, and influencing transcription and translation. Our research involved an extensive analysis of circRNAs ribo-seq data, complemented by mass spectrometry, Western blotting, and immunofluorescence to validate the encoding of circR-127aa by circRACK1. We explored the functional impact of circR-127aa, examining its effects on cell proliferation, apoptosis, and tumor formation in nude mice. A critical aspect of this study was investigating the interaction between circR-127aa and Vimentin, a significant player in cytoskeleton remodeling and cellular mobility during epithelial-mesenchymal transition (EMT). The findings reveal that the circRACK1-encoded peptide functions as a tumor suppressor, facilitating Vimentin ubiquitination, highlighting its potential as a novel therapeutic target and biomarker in GC treatment. In conclusion, this research unveils a groundbreaking role of the circRACK1-encoded peptide, circR-127aa, in GC, emphasizing its tumor-suppressing function through the ubiquitination of Vimentin. This discovery enhances our understanding of GC progression and presents circR-127aa as a valuable candidate for therapeutic strategies and as a biomarker in GC treatment.