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Knockdown of lncRNA HOXA-AS3 Suppresses the Progression of Atherosclerosis via Sponging miR-455-5p
Drug Design, Development and Therapy ( IF 4.8 ) Pub Date : 2020-09-09 , DOI: 10.2147/dddt.s249830 Kui Chi 1 , Jinwen Zhang 1 , Huanhuan Sun 1 , Yang Liu 1 , Ye Li 2 , Tao Yuan 1 , Feng Zhang 1
Drug Design, Development and Therapy ( IF 4.8 ) Pub Date : 2020-09-09 , DOI: 10.2147/dddt.s249830 Kui Chi 1 , Jinwen Zhang 1 , Huanhuan Sun 1 , Yang Liu 1 , Ye Li 2 , Tao Yuan 1 , Feng Zhang 1
Affiliation
Background: 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.
Materials and Methods: 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.
Results: 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.
Conclusion: 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.
中文翻译：
敲除 lncRNA HOXA-AS3 通过海绵化 miR-455-5p 抑制动脉粥样硬化的进展
背景：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) 涉及多种疾病，包括动脉粥样硬化。发现 LncRNA HOXA-AS3 在动脉粥样硬化中显着上调。然而，HOXA-AS3在动脉粥样硬化发生发展过程中的生物学功能仍不清楚。
材料和方法：用氧化低密度脂蛋白 (oxLDL) 处理人血管内皮细胞 (HUVEC) 以在体外模拟动脉粥样硬化。分别通过 RT-qPCR 和蛋白质印迹检测 HUVEC 中的基因和蛋白质表达。通过CCK-8和Ki67染色测试细胞增殖。通过流式细胞术测量细胞凋亡和周期。此外，HOXA-AS3 和 miR-455-5p 之间的相关性通过双荧光素酶报告测定和 RNA 下拉得到证实。最后，建立了体内动脉粥样硬化模型，以确认HOXA-AS3在体内动脉粥样硬化发展过程中的功能。
结果：LncRNA HOXA-AS3 在 oxLDL 处理的 HUVEC 中上调。此外，通过敲低 HOXA-AS3 可显着逆转 oxLDL 诱导的 HUVEC 生长抑制。一致地，oxLDL显着诱导HUVEC中的G1期停滞，而HOXA-AS3 siRNA极大地逆转了这种现象。此外，HOXA-AS3 的下调通过介导 miR-455-5p/p27 Kip1 轴显着抑制动脉粥样硬化的进展。此外，HOXA-AS3的沉默显着缓解了体内动脉粥样硬化的症状。
结论： HOXA-AS3的下调通过调节miR-455-5p/p27 Kip1轴显着抑制动脉粥样硬化的进展。因此，HOXA-AS3 可能作为治疗动脉粥样硬化的潜在靶点。
更新日期：2020-09-10
Materials and Methods: 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.
Results: 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.
Conclusion: 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.
中文翻译：
敲除 lncRNA HOXA-AS3 通过海绵化 miR-455-5p 抑制动脉粥样硬化的进展
背景：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) 涉及多种疾病，包括动脉粥样硬化。发现 LncRNA HOXA-AS3 在动脉粥样硬化中显着上调。然而，HOXA-AS3在动脉粥样硬化发生发展过程中的生物学功能仍不清楚。
材料和方法：用氧化低密度脂蛋白 (oxLDL) 处理人血管内皮细胞 (HUVEC) 以在体外模拟动脉粥样硬化。分别通过 RT-qPCR 和蛋白质印迹检测 HUVEC 中的基因和蛋白质表达。通过CCK-8和Ki67染色测试细胞增殖。通过流式细胞术测量细胞凋亡和周期。此外，HOXA-AS3 和 miR-455-5p 之间的相关性通过双荧光素酶报告测定和 RNA 下拉得到证实。最后，建立了体内动脉粥样硬化模型，以确认HOXA-AS3在体内动脉粥样硬化发展过程中的功能。
结果：LncRNA HOXA-AS3 在 oxLDL 处理的 HUVEC 中上调。此外，通过敲低 HOXA-AS3 可显着逆转 oxLDL 诱导的 HUVEC 生长抑制。一致地，oxLDL显着诱导HUVEC中的G1期停滞，而HOXA-AS3 siRNA极大地逆转了这种现象。此外，HOXA-AS3 的下调通过介导 miR-455-5p/p27 Kip1 轴显着抑制动脉粥样硬化的进展。此外，HOXA-AS3的沉默显着缓解了体内动脉粥样硬化的症状。
结论： HOXA-AS3的下调通过调节miR-455-5p/p27 Kip1轴显着抑制动脉粥样硬化的进展。因此，HOXA-AS3 可能作为治疗动脉粥样硬化的潜在靶点。
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