Feng Liuliu, Liu Tianhua, Shi Jun, Wang Yu, Yang Yuya, Xiao Wenyin, Bai Yanyan
Department of Cardiology, Shidong Hospital, 200438, Shanghai, China.
Department of Cardiology, Shidong Hospital, No. 999 Shiguang Road, Yangpu District, 200438, Shanghai, China.
Open Med (Wars). 2023 Aug 30;18(1):20230751. doi: 10.1515/med-2023-0751. eCollection 2023.
The aim of our study is to disclose the role and underlying molecular mechanisms of circular RNA ubiquitin protein ligase E3 component -recognin 4 (circ-UBR4) in atherosclerosis (AS). Our data showed that circ-UBR4 expression was upregulated in AS patients and oxidized low-density lipoprotein (ox-LDL)-induced vascular smooth muscle cells (VSMCs) compared with healthy volunteer and untreated VSMCs. In addition, ox-LDL stimulated proliferation, migration, and inflammation but decreased apoptosis in VSMCs, which were overturned by the inhibition of circ-UBR4. miR-515-5p was sponged by circ-UBR4, and its inhibitor reversed the inhibitory effect of circ-UBR4 knockdown on proliferation, migration, and inflammation in ox-LDL-induced VSMCs. Insulin-like growth factor2 (IGF2) was a functional target of miR-515-5p, and overexpression of IGF2 reversed the suppressive effect of miR-515-5p on ox-LDL-stimulated VSMCs proliferation, migration, and inflammation. Collectively, circ-UBR4 knockdown decreased proliferation, migration, and inflammation but stimulated apoptosis in ox-LDL-induced VSMCs by targeting the miR-515-5p/IGF2 axis.
我们研究的目的是揭示环状RNA泛素蛋白连接酶E3组分识别蛋白4（circ-UBR4）在动脉粥样硬化（AS）中的作用及潜在分子机制。我们的数据显示，与健康志愿者和未处理的血管平滑肌细胞（VSMC）相比，circ-UBR4在AS患者和氧化型低密度脂蛋白（ox-LDL）诱导的VSMC中表达上调。此外，ox-LDL刺激VSMC增殖、迁移和炎症反应，但降低其凋亡，而circ-UBR4的抑制可逆转这些变化。circ-UBR4可吸附miR-515-5p，其抑制剂可逆转circ-UBR4敲低对ox-LDL诱导的VSMC增殖、迁移和炎症的抑制作用。胰岛素样生长因子2（IGF2）是miR-515-5p的功能靶点，IGF2的过表达可逆转miR-515-5p对ox-LDL刺激的VSMC增殖、迁移和炎症的抑制作用。总之，circ-UBR4敲低通过靶向miR-515-5p/IGF2轴，降低ox-LDL诱导的VSMC增殖、迁移和炎症反应，但促进其凋亡。
