Department of Cardiovascular Surgery, Guizhou Provincial People's Hospital, No.83, East Zhongshan Road, Guiyang, 550002, Guizhou Province, People's Republic of China.
Biochem Genet. 2021 Oct;59(5):1158-1172. doi: 10.1007/s10528-021-10053-y. Epub 2021 Mar 9.
Pulmonary arterial hypertension (PAH) seriously threatens the elder people. Long non-coding RNAs (lncRNAs) are involved in multiple diseases. However, the study of the lncRNAs in the occurrence of PAH is just beginning. For this, we sought to explore the biological function of lncRNA HOXA cluster antisense RNA 3 (HOXA-AS3) in PAH. Hypoxia (HYP) was used to mimic in vitro model of PAH. Gene and protein expressions in cells were detected by q-PCR and Western blotting, respectively. In addition, cell proliferation and viability were tested by CCK-8 and MTT assay. Cell apoptosis was measured by flow cytometry. Wound healing was used to detect cell migration. Furthermore, the connection of HOXA-AS3, miR-675-3p, and phosphodiesterase 5A (PDE5A) was verified by dual-luciferase report assay. HOXA-AS3 and PDE5A were upregulated in human pulmonary artery smooth muscle cells (HPASMCs) in the presence of HYP, while miR-675-3p was downregulated. Moreover, knockdown of HOXA-AS3 suppressed the growth and migration of HPASMCs, but induced the apoptosis. Overexpression of miR-675-3p achieved the same effect. MiR-675-3p inhibitor or overexpression of PDE5A notably reversed the inhibitory effect of HOXA-AS3 knockdown on PAH. Finally, HOXA-AS3 could sponge miR-675-3p, and PDE5A was directly targeted by miR-675-3p. HOXA-AS3 increased the development of PAH via regulation of miR-675-3p/PDE5 axis, which could be the potential biomarker for treatment of PAH.
肺动脉高压（PAH）严重威胁老年人健康。长链非编码 RNA（lncRNA）参与多种疾病。然而，lncRNA 在 PAH 发生中的研究才刚刚开始。为此，我们试图探讨 lncRNA HOXA 簇反义 RNA 3（HOXA-AS3）在 PAH 中的生物学功能。采用低氧（HYP）模拟体外 PAH 模型。通过 q-PCR 和 Western blot 分别检测细胞中的基因和蛋白表达。此外，通过 CCK-8 和 MTT 测定检测细胞增殖和活力。通过流式细胞术检测细胞凋亡。通过划痕实验检测细胞迁移。进一步通过双荧光素酶报告实验验证 HOXA-AS3、miR-675-3p 和磷酸二酯酶 5A（PDE5A）之间的联系。在存在 HYP 的情况下，人肺动脉平滑肌细胞（HPASMCs）中 HOXA-AS3 和 PDE5A 上调，而 miR-675-3p 下调。此外，敲低 HOXA-AS3 抑制 HPASMCs 的生长和迁移，但诱导细胞凋亡。过表达 miR-675-3p 可达到相同效果。miR-675-3p 抑制剂或过表达 PDE5A 显著逆转了 HOXA-AS3 敲低对 PAH 的抑制作用。最后，HOXA-AS3 可以海绵吸附 miR-675-3p，而 PDE5A 可直接靶向 miR-675-3p。HOXA-AS3 通过调节 miR-675-3p/PDE5 轴促进 PAH 的发展，这可能是 PAH 治疗的潜在生物标志物。
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