Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Mesquite Rehabilitation Institute, Mesquite, Texas, USA.
Sci Rep. 2020 Feb 24;10(1):3261. doi: 10.1038/s41598-020-60025-2.
Infantile hemangiomas (IHs) are the most common benign tumors in early childhood. They show a distinctive mechanism of tumor growth in which a rapid proliferative phase is followed by a regression phase (involution). Propranolol is an approved treatment for IHs, but its mechanism of action remains unclear. We integrated and harmonized microRNA and mRNA transcriptome data from newly generated microarray data on IHs with publicly available data on toxicological transcriptomics from propranolol exposure, and with microRNA data from IHs and propranolol exposure. We identified subsets of putative biomarkers for proliferation and involution as well as a small set of putative biomarkers for propranolol's mechanism of action for IHs, namely EPAS1, LASP1, SLC25A23, MYO1B, and ALDH1A1. Based on our integrative data approach and confirmatory experiments, we concluded that hypoxia in IHs is regulated by EPAS1 (HIF-2α) instead of HIF-1α, and also that propranolol-induced apoptosis in endothelial cells may occur via mitochondrial stress.
婴儿血管瘤（IHs）是儿童早期最常见的良性肿瘤。它们表现出一种独特的肿瘤生长机制，其中快速增殖期后是退化期（退化）。普萘洛尔是 IHs 的一种已批准的治疗方法，但它的作用机制仍不清楚。我们整合并协调了新生成的 IH 微阵列数据的 microRNA 和 mRNA 转录组数据，以及普萘洛尔暴露的毒理学转录组学的公开数据，以及 IH 和普萘洛尔暴露的 microRNA 数据。我们确定了增殖和退化的潜在生物标志物亚群，以及一小部分 IH 普萘洛尔作用机制的潜在生物标志物，即 EPAS1、LASP1、SLC25A23、MYO1B 和 ALDH1A1。基于我们的综合数据方法和验证实验，我们得出结论，IHs 中的缺氧是由 EPAS1（HIF-2α）而不是 HIF-1α 调节的，并且普萘洛尔诱导内皮细胞中的细胞凋亡可能通过线粒体应激发生。
