EPAS1 对 miRNA 调控的抵抗导致人内皮细胞在低氧条件下 HIF-2 的表达延长。

EPAS1 resistance to miRNA-based regulation contributes to prolonged expression of HIF-2 during hypoxia in human endothelial cells.

机构信息

International Research Agenda 3P- Medicine Laboratory, Medical University of Gdansk, Gdansk, Poland.

Independent Researcher.

出版信息

Gene. 2023 Jun 5;868:147376. doi: 10.1016/j.gene.2023.147376. Epub 2023 Mar 18.

DOI:10.1016/j.gene.2023.147376

PMID:36934786

Abstract

The cellular adaptation to hypoxia is regulated by hypoxia inducible factors: HIF-1 and HIF-2. HIF-1 mediates response to acute hypoxia, whereas HIF-2 allows adaptation to chronic oxygen deprivation. The hypoxic transition from HIF-1 to HIF-2 is possible due to the low stability of HIF-1α subunit transcript (HIF1A) and the stable mRNA of HIF-2α (EPAS1). Notably, although many micro-RNAs (miRNAs) that regulate endothelial HIF-1 levels during hypoxia have been identified, in case of HIF-2, no analogous ones have been found so far. In this work, using different methods, we tested 23 microRNA that were predicted to interact with the EPAS1 transcript (18 of which were induced during prolonged hypoxia), and we demonstrated that none of them were functional in vitro. This suggests that HIF-2α transcript is much less prone to miRNA-related destabilization during hypoxia.

摘要

细胞对缺氧的适应受缺氧诱导因子（HIF）的调节：HIF-1 和 HIF-2。HIF-1 介导对急性缺氧的反应，而 HIF-2 允许对慢性缺氧的适应。由于 HIF-1α 亚基转录物（HIF1A）的低稳定性和 HIF-2α（EPAS1）的稳定 mRNA，HIF-1 向 HIF-2 的缺氧转换成为可能。值得注意的是，尽管已经鉴定出许多在缺氧期间调节内皮细胞 HIF-1 水平的 microRNA（miRNA），但在 HIF-2 的情况下，迄今为止尚未发现类似的 miRNA。在这项工作中，我们使用不同的方法测试了 23 种预测与 EPAS1 转录物相互作用的 microRNA（其中 18 种在长时间缺氧期间被诱导），并证明它们在体外均没有功能。这表明 HIF-2α 转录物在缺氧期间更不容易受到 miRNA 相关的不稳定性的影响。