A Novel Hidden Protein p-414aa Encoded by circSETD2(14,15) Inhibits Vascular Remodeling

The phenotypic switching of vascular smooth muscle cells (VSMCs) leads to neointimal hyperplasia, which is the underlying cause of vascular remodeling diseases such as atherosclerosis and hypertension. Novel hidden proteins encoded by circular RNAs (circRNAs) play crucial roles in disease progression. Our study identified a new protein derived from a circRNA in VSMCs and demonstrated its potential role in regulating vascular remodeling. We discovered a novel hidden protein, p-414aa, encoded by circSETD2(14,15), which can inhibit vascular remodeling. Both circSETD2(14,15) and p-414aa may serve as potential therapeutic targets for vascular remodeling diseases. In this study, we demonstrated that the new protein p-414aa encoded by circSETD2(14,15) inhibits VSMC proliferation and neointimal hyperplasia through the HuR/C-FOS axis. In summary, our data provide a molecular framework for the phenotypic switching of vascular smooth muscle cells. To identify potential mRNA targets regulated by p-414aa, we performed RNA sequencing (RNA-seq) analysis in human aortic smooth muscle cells (HASMCs) with or without p-414aa overexpression. For overexpression, we used the pcDNA3.1(+) plasmid to overexpress p-414aa in HASMCs, with the pcDNA3.1-EGFP plasmid serving as a control.