Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Radiology, Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen, China.
J Cell Mol Med. 2020 Dec;24(24):14231-14246. doi: 10.1111/jcmm.16040. Epub 2020 Oct 30.
Acute coronary syndrome caused by the rupture of atherosclerotic plaques is one of the primary causes of cerebrovascular and cardiovascular events. Neovascularization within the plaque is closely associated with its stability. Long non-coding RNA (lncRNA) serves a crucial role in regulating vascular endothelial cells (VECs) proliferation and angiogenesis. In this study, we identified lncRNA HCG11, which is highly expressed in patients with vulnerable plaque compared with stable plaque. Then, functional experiments showed that HCG11 reversed high glucose-induced vascular endothelial injury through increased cell proliferation and tube formation. Meanwhile, vascular-related RNA-binding protein QKI5 was greatly activated. Luciferase reporter assays and RNA-binding protein immunoprecipitation (RIP) assays verified interaction between them. Interestingly, HCG11 can also positively regulated by QKI5. Bioinformatics analysis and luciferase reporter assays showed HCG11 can worked as a competing endogenous RNA by sponging miR-26b-5p, and QKI5 was speculated as the target of miR-26b-5p. Taken together, our findings revered that the feedback loop of lncRNA HCG11/miR-26b-5p/QKI-5 played a vital role in the physiological function of HUVECs, and this also provide a potential target for therapeutic strategies of As.
动脉粥样硬化斑块破裂引起的急性冠状动脉综合征是脑血管和心血管事件的主要原因之一。斑块内的新生血管与斑块的稳定性密切相关。长链非编码 RNA（lncRNA）在调节血管内皮细胞（VEC）增殖和血管生成方面起着至关重要的作用。在本研究中，我们鉴定出在易损斑块患者中高表达的 lncRNA HCG11。然后，功能实验表明 HCG11 通过增加细胞增殖和管形成来逆转高葡萄糖诱导的血管内皮损伤。同时，血管相关 RNA 结合蛋白 QKI5 被极大地激活。荧光素酶报告基因实验和 RNA 结合蛋白免疫沉淀（RIP）实验验证了它们之间的相互作用。有趣的是，HCG11 也可以被 QKI5 正向调控。生物信息学分析和荧光素酶报告基因实验表明，HCG11 可以作为 miR-26b-5p 的竞争性内源性 RNA，而 QKI5 被推测为 miR-26b-5p 的靶基因。总之，我们的研究结果表明，lncRNA HCG11/miR-26b-5p/QKI-5 的反馈环在 HUVECs 的生理功能中起着重要作用，这也为 As 的治疗策略提供了一个潜在的靶点。
