circSCAF11 Attenuates TGF-β/SMAD2/3 Signaling to Suppress Colorectal Cancer Progression

Circular RNAs with high stability offer potential advantages for developing therapeutic agents against cancers. CircSCAF11 has been reported to be downregulated in CRC, yet its functional mechanisms remain largely unknown. In this study, we demonstrate that circSCAF11 is a genuine circular RNA generated by back-splicing of exon 5 of the SCAF11 pre-mRNA. We further show that ectopic expression of circSCAF11 inhibits CRC cell proliferation and colony formation. Moreover, its overexpression suppresses the intracellular TGF-β/Smad2/3 signaling pathway and attenuates the epithelial–mesenchymal transition (EMT), migration, and invasion activated by this pathway, while promoting cell apoptosis through the same pathway. In vivo experiments further confirmed that circSCAF11 suppresses CRC tumor growth in nude mouse xenograft models. Collectively, our findings provide novel theoretical insights into the development of circSCAF11-based therapeutic strategies for CRC.