Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Department of Cardiovascular Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Bioengineered. 2022 Mar;13(3):5987-5998. doi: 10.1080/21655979.2022.2039467.
Circular RNAs, a class of circularly closed non-coding RNAs, play essential roles in the formation of atherosclerosis, which is a frequent cause of cardiovascular and cerebrovascular diseases. Although many circular RNAs are found to be involved in the progression of atherosclerosis, more circular RNA regulators still need to be identified, to improve the understanding of the regulatory networks of atherosclerosis. Here, we found that hsa_circ_0008896 was significantly up-regulated in both and atherosclerosis models, indicating hsa_circ_0008896 was involved in the progression of atherosclerosis. Further functional analyses confirmed that knockdown of hsa_circ_0008896 decreased proliferation, migration, and invasion of VSMCs. In addition, we conducted bioinformatics analysis and found that hsa-miR-633 could directly bind to hsa_circ_0008896, which was confirmed by RNA immune-precipitation (RIP) assays. Results of proliferation, migration, and invasion assays showed that hsa-miR-633 inhibitor reversed the si-circ_0008896 phenotypes, indicating that hsa_circ_0008896 functionally bound to hsa-miR-633. At last, combining bioinformatics and experimental analyses, we found the protein target of hsa_circ_0008896/hsa-miR-633, CDC20B (cell division cycle 20B). The expression level of CDC20B was regulated by hsa-miR-633, and knockdown of CDC20B decreased proliferation, migration, and invasion of VSMCs. Taken together, hsa_circ_0008896 regulated the expression of CDC20B by sponging hsa-miR-633, and then enhanced proliferation, migration, and invasion of VSMCs to promote the progression of atherosclerosis.
环状 RNA 是一类环状闭合的非编码 RNA，在动脉粥样硬化的形成中发挥着重要作用，动脉粥样硬化是心血管和脑血管疾病的常见病因。虽然已经发现许多环状 RNA 参与了动脉粥样硬化的进展，但仍需要鉴定更多的环状 RNA 调节因子，以提高对动脉粥样硬化调控网络的认识。在这里，我们发现 hsa_circ_0008896 在 和 动脉粥样硬化模型中均显著上调，表明 hsa_circ_0008896 参与了动脉粥样硬化的进展。进一步的功能分析证实，hsa_circ_0008896 的敲低降低了 VSMCs 的增殖、迁移和侵袭。此外，我们进行了生物信息学分析，发现 hsa-miR-633 可以直接与 hsa_circ_0008896 结合，这通过 RNA 免疫沉淀 (RIP) 实验得到了证实。增殖、迁移和侵袭实验的结果表明，hsa-miR-633 抑制剂逆转了 si-circ_0008896 的表型，表明 hsa_circ_0008896 与 hsa-miR-633 功能结合。最后，通过生物信息学和实验分析相结合，我们找到了 hsa_circ_0008896/hsa-miR-633 的蛋白靶标 CDC20B（细胞分裂周期 20B）。CDC20B 的表达水平受 hsa-miR-633 调节，敲低 CDC20B 降低了 VSMCs 的增殖、迁移和侵袭。总之，hsa_circ_0008896 通过海绵吸附 hsa-miR-633 调节 CDC20B 的表达，进而增强 VSMCs 的增殖、迁移和侵袭，促进动脉粥样硬化的进展。
