Nersisyan S A, Shkurnikov M Yu, Knyazev E N
Faculty of Biology and Biotechnology, National Research University Higher School of Economics, Moscow, Russia.
Faculty of Mechanics and Mathematics, Moscow State University, Moscow, Russia.
Dokl Biochem Biophys. 2020 Jul;493(1):205-207. doi: 10.1134/S1607672920040110. Epub 2020 Sep 7.
One of the main complications of pregnancy and causes of maternal and perinatal mortality is preeclampsia. The pathophysiology of preeclampsia is associated with the development of placenta and fetal hypoxia and secretion of a number of effective molecules. The human choriocarcinoma cell line BeWo b30 is often used as a model of the placental barrier. It was shown that oxyquinoline derivatives can mimic hypoxia by suppressing HIF-prolyl hydroxylases and the accumulation of HIF-1α. This effect also leads to a change in the expression of microRNAs and their target genes. However, with hypoxia in cells, not only the level of individual miRNAs but also the ratio of miRNA isoforms (isomiRs) can change, presumably due to inaccuracies in the work of the Drosha and Dicer enzymes. In this work, we showed a change in the expression of the factors involved in the maturation of miRNAs when simulating hypoxia in BeWo b30 cells with an oxyquinoline derivative, which may be one of the causes for the change in the ratio of miRNA isoforms.
子痫前期是妊娠的主要并发症之一，也是孕产妇和围产期死亡的原因。子痫前期的病理生理学与胎盘发育、胎儿缺氧以及多种有效分子的分泌有关。人绒毛膜癌细胞系BeWo b30常被用作胎盘屏障模型。研究表明，氧喹啉衍生物可通过抑制HIF-脯氨酰羟化酶和HIF-1α的积累来模拟缺氧。这种效应还会导致微小RNA及其靶基因表达的改变。然而，在细胞缺氧时，不仅单个微小RNA的水平会发生变化，微小RNA异构体（isomiRs）的比例也可能改变，推测这是由于Drosha和Dicer酶工作不准确所致。在本研究中，我们发现用氧喹啉衍生物模拟BeWo b30细胞缺氧时，参与微小RNA成熟的因子表达发生了变化，这可能是微小RNA异构体比例改变的原因之一。
