YBX1 Modulates Intimal Hyperplasia by Regulating Expression and Alternative Splicing of Cell Cycle Associated Genes in RASMCs

Abstract

YBX1, a DNA-/RNA-binding protein, is implicated in various diseases, yet its role in intimal hyperplasia (IH) remains unclear. This study investigates YBX1's function in rat aortic smooth muscle cells (RASMCs) through knockdown experiments. Results show that YBX1 knockdown reduces cell proliferation and migration while inducing apoptosis. ELISA and western blot analyses revealed increased levels of the anti-inflammatory factor IL10 and markers for phenotypic transformation, Calponin and Myocardin. Transcriptome sequencing identified 1598 differentially expressed genes (DEGs), with 347 upregulated and 1251 downregulated. Upregulated DEGs were linked to pathways like ECM-receptor interaction and Wnt signalling, while downregulated genes involved cell cycle and p53 signalling. Additionally, 629 significant alternative splicing events were noted, primarily affecting pathways related to cell division and migration. Integrated analysis of YBX1-bound RNAs and RNA-seq data highlighted key DEGs, such as CCNB1 and TPM1, which are crucial for vascular cell behaviour. This study underscores YBX1's vital role in RASMCs and suggests potential therapeutic targets for IH treatment.

Keywords: YBX1; alternative splicing; cell cycle; cell migration; intimal hyperplasia.