Emergency Department, Hainan People's Hospital, Haikou, China.
Eur Rev Med Pharmacol Sci. 2020 Sep;24(17):9022-9029. doi: 10.26355/eurrev_202009_22845.
To elucidate the potential biological functions of long non-coding RNA (lncRNA) MIAT in the development of hypoxic pulmonary hypertension (HPH) and the underlying mechanism.
Twenty Sprague Dawley (SD) rats were randomly assigned into normoxia group (n=10) and hypoxia group (n=10), respectively. In vivo HPH model in rats was established by hypoxic induction. Expression levels of MIAT and miR-29a-5p in rats were detected. Meanwhile, hemodynamic indicators in rats were examined. In vitro HPH model was conducted in hypoxia-induced HPAECs. The interaction between MIAT and miR-29a-5p was assessed by Dual-Luciferase reporter assay. Moreover, their regulatory effects on viability, migratory ability, oxidative stress, and the Nrf2 pathway in hypoxia-induced HPAECs were examined.
MIAT was upregulated in both in vivo and in vitro HPH models, while miR-29a-5p was downregulated. Knockdown of MIAT suppressed viability, migratory ability, and oxidative stress in hypoxia-induced HPAECs. MiR-29a-5p was the target gene binding MIAT, and silence of miR-29a-5p partially relieved the inhibitory effects of MIAT on the above regulations in HPAECs.
MIAT promotes proliferative and migratory abilities, as well as oxidative stress in hypoxia-induced HPAECs by targeting miR-29a-5p, thus aggravating the development of HPH.
阐明长链非编码 RNA（lncRNA）MIAT 在低氧性肺动脉高压（HPH）发展中的潜在生物学功能及其潜在机制。
将 20 只 Sprague Dawley（SD）大鼠随机分为常氧组（n=10）和低氧组（n=10）。通过低氧诱导建立大鼠体内 HPH 模型。检测大鼠 MIAT 和 miR-29a-5p 的表达水平。同时，检测大鼠血流动力学指标。在缺氧诱导的人肺动脉内皮细胞（HPAECs）中建立体外 HPH 模型。通过双荧光素酶报告基因检测评估 MIAT 和 miR-29a-5p 之间的相互作用。此外，还检测了它们对缺氧诱导的 HPAECs 活力、迁移能力、氧化应激和 Nrf2 通路的调节作用。
在体内和体外 HPH 模型中，MIAT 均上调，而 miR-29a-5p 下调。MIAT 敲低抑制了缺氧诱导的 HPAECs 的活力、迁移能力和氧化应激。miR-29a-5p 是 MIAT 的靶基因结合物，沉默 miR-29a-5p 部分缓解了 MIAT 对 HPAECs 上述调节的抑制作用。
MIAT 通过靶向 miR-29a-5p 促进缺氧诱导的 HPAECs 的增殖和迁移能力以及氧化应激，从而加重 HPH 的发展。
