Department of Vascular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, People's Republic of China.
Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, People's Republic of China.
Drug Des Devel Ther. 2020 Sep 9;14:3651-3662. doi: 10.2147/DDDT.S249830. eCollection 2020.
Atherosclerosis can lead to multiple cardiovascular diseases, especially myocardial infarction. Long noncoding RNAs (lncRNAs) are involved in multiple diseases, including atherosclerosis. LncRNA HOXA-AS3 was found to be notably upregulated in atherosclerosis. However, the biological function of HOXA-AS3 during the occurrence and development of atherosclerosis remains unclear.
Human vascular endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (oxLDL) to mimic atherosclerosis in vitro. Gene and protein expressions in HUVECs were detected by RT-qPCR and Western blot, respectively. Cell proliferation was tested by CCK-8 and Ki67 staining. Cell apoptosis and cycle were measured by flow cytometry. Additionally, the correlation between HOXA-AS3 and miR-455-5p was confirmed by dual luciferase report assay and RNA pull-down. Finally, in vivo model of atherosclerosis was established to confirm the function of HOXA-AS3 during the development of atherosclerosis in vivo.
LncRNA HOXA-AS3 was upregulated in oxLDL-treated HUVECs. In addition, oxLDL-induced growth inhibition of HUVECs was significantly reversed by knockdown of HOXA-AS3. Consistently, oxLDL notably induced G1 arrest in HUVECs, while this phenomenon was greatly reversed by HOXA-AS3 siRNA. Furthermore, downregulation of HOXA-AS3 notably inhibited the progression of atherosclerosis through mediation of miR-455-5p/p27 Kip1 axis. Besides, silencing of HOXA-AS3 notably relieved the symptom of atherosclerosis in vivo.
Downregulation of HOXA-AS3 significantly suppressed the progression of atherosclerosis via regulating miR-455-5p/p27 Kip1 axis. Thus, HOXA-AS3 might serve as a potential target for the treatment of atherosclerosis.
动脉粥样硬化可导致多种心血管疾病，尤其是心肌梗死。长链非编码 RNA（lncRNA）参与多种疾病，包括动脉粥样硬化。研究发现 lncRNA HOXA-AS3 在动脉粥样硬化中显著上调。然而，HOXA-AS3 在动脉粥样硬化发生发展过程中的生物学功能尚不清楚。
体外采用氧化型低密度脂蛋白（oxLDL）处理人血管内皮细胞（HUVECs）模拟动脉粥样硬化。分别采用 RT-qPCR 和 Western blot 检测 HUVECs 中的基因和蛋白表达。采用 CCK-8 和 Ki67 染色检测细胞增殖。采用流式细胞术检测细胞凋亡和周期。此外，通过双荧光素酶报告实验和 RNA 下拉实验证实了 HOXA-AS3 与 miR-455-5p 的相关性。最后，建立了动脉粥样硬化的体内模型，以证实 HOXA-AS3 在体内动脉粥样硬化发展过程中的作用。
lncRNA HOXA-AS3 在 oxLDL 处理的 HUVECs 中上调。此外，HOXA-AS3 的敲低显著逆转了 oxLDL 诱导的 HUVECs 生长抑制。一致地，oxLDL 显著诱导 HUVECs 的 G1 期阻滞，而 HOXA-AS3 siRNA 则大大逆转了这一现象。此外，下调 HOXA-AS3 通过调节 miR-455-5p/p27 Kip1 轴显著抑制了动脉粥样硬化的进展。此外，HOXA-AS3 的沉默显著缓解了体内动脉粥样硬化的症状。
下调 HOXA-AS3 通过调节 miR-455-5p/p27 Kip1 轴显著抑制了动脉粥样硬化的进展。因此，HOXA-AS3 可能成为治疗动脉粥样硬化的潜在靶点。
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