Circular RNA UVRAG Mediated by Alternative Splicing Factor NOVA1 Regulates Adhesion and Migration of Vascular Smooth Muscle Cells

可变剪接因子NOVA1介导的环状RNA UVRAG调控血管平滑肌细胞粘附和迁移

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作者:Ze Liu, Yue Lou, Jia-Chen Cui, Yi Chen, Ji-Ting Liu, Ying Yuan, Yue Han, Yun-Long Huo, Ying-Xin Qi, Zong-Lai Jiang, Qing-Ping Yao

Abstract

The movement of abnormal vascular smooth muscle cells (VSMCs) contributes to intimal hyperplasia in vein graft disease. Circular RNAs (circRNAs) are single stranded RNAs with 3' and 5' ends covalently joined together. They have been shown to regulate cell function in many diseases. NOVA1 is considered to be a brain-specific splicing factor that plays an important role in the nervous system and cancer. The role of NOVA1 in VSMCs remains unclear. In the present study, transcriptome sequencing was used to identify differentially expressed circRNAs in the rat vein graft model. A novel circRNA, circUVRAG, was decreased in the grafted vein and stably located in the cytoplasm. Knockdown of circUVRAG suppressed VSMC adhesion and migration. In addition, we demonstrated that the alternative splicing factor NOVA1 co-located with UVRAG pre-mRNA in the nucleus and modulated the production of circUVRAG. These new discoveries may serve as a potential means to treat intimal hyperplasia after vein grafts.

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