Lim Jiwoo, Choi Youn-Hee, Shim So-Yeon
Department of Physiology, Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul 07804, Korea.
Department of Pediatrics, College of Medicine, Ewha Womans University, Seoul 07804, Korea.
Transl Clin Pharmacol. 2024 Mar;32(1):18-29. doi: 10.12793/tcp.2024.32.e3. Epub 2024 Feb 21.
Intraventricular hemorrhage (IVH) is a cause of morbidity and mortality in preterm infants and is strongly associated with adverse neurological outcomes. The incidence of severe IVH (grade 3 or 4) has persisted despite the overall decline in IVH. IVH has been attributed to changes in cerebral blood flow to the immature germinal matrix microvasculature. The cascade of adverse events following IVH includes inflammation, white matter injury, and delayed oligodendrial maturation. In this study, we aimed to identify long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) expression in the peripheral blood of preterm infants with IVH compared to normal controls, resulting in the finding of novel biomarkers for IVH. We conducted transcriptome sequencing and small RNA sequencing for identifying differential expression of RNA in preterm infants with IVH. We identified differentially expressed 47 lncRNAs, 95 miRNAs, and 1,370 mRNAs in preterm infants with IVH compared to normal control. Particularly, lncRNA H19 exhibited significantly high expression in preterm infants with IVH. The functional analysis revealed that differentially expressed RNAs in preterm infants with IVH were associated with ferroptosis, heme metabolism, and immune response such as lymphocyte activation and interferon response. In conclusion, these results demonstrate the potential of lncRNA, miRNA, mRNA as possible diagnostic and prognostic biomarkers for IVH.
脑室内出血(IVH)是早产儿发病和死亡的一个原因,并且与不良神经学预后密切相关。尽管IVH的总体发生率有所下降,但严重IVH(3级或4级)的发生率一直居高不下。IVH被认为是由于流向未成熟生发基质微血管的脑血流发生变化所致。IVH后的一系列不良事件包括炎症、白质损伤和少突胶质细胞成熟延迟。在本研究中,我们旨在确定与正常对照组相比,IVH早产儿外周血中长链非编码RNA(lncRNA)、微小RNA(miRNA)和信使RNA(mRNA)的表达情况,从而发现IVH的新型生物标志物。我们进行了转录组测序和小RNA测序,以确定IVH早产儿中RNA的差异表达。与正常对照组相比,我们在IVH早产儿中鉴定出47种差异表达的lncRNA、95种miRNA和1370种mRNA。特别是,lncRNA H19在IVH早产儿中表现出显著高表达。功能分析显示IVH早产儿中差异表达的RNA与铁死亡、血红素代谢以及免疫反应如淋巴细胞活化和干扰素反应相关。总之,这些结果证明lncRNA、miRNA、mRNA作为IVH潜在的诊断和预后生物标志物的可能性。