Factors Involved in miRNA Processing Change Its Expression Level during Imitation of Hypoxia in BeWo b30 Cells
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HEMISTRY, BIOPHYSICS, AND MOLECULAR BIOLOGY
Factors Involved in miRNA Processing Change Its Expression Level during Imitation of Hypoxia in BeWo b30 Cells S. A. Nersisyana,b, M. Yu. Shkurnikovc, and E. N. Knyazevd,e,* Presented by Academician S.I. Kolesnikov Received March 30, 2020; revised April 17, 2020; accepted April 17, 2020
Abstract—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. Keywords: Drosha, Dicer, DGCR8, TARBP2, placenta, choriocarcinoma, BeWo, miRNA, miRNA isoforms, isomiRs DOI: 10.1134/S1607672920040110
One of the main complications of pregnancy and the causes of maternal and perinatal mortality is preeclampsia, a pathology whose pathogenesis is associated with disturbance of the utero-placental blood flow and the development of placental and fetal hypoxia. According to one theory, placental hypoxia is the primary factor leading to the development of this disease: apparently, at the trophoblast hypoxia, various effector molecules that trigger pathological changes can be released into the bloodstream of the Abbreviations: dsRNA, double-stranded RNA, FDR, false discovery rate (level of false positive results), HIF, hypoxiainduced factor, DMSO, dimethyl sulfoxide, FITC, fluorescein isothiocyanate.
a Faculty
of Biology and Biotechnology, National Research University Higher School of Economics, Moscow, Russia b Faculty of Mechanics and Mathematics, Moscow State University, Moscow, Russia c Hertsen Moscow Oncology Research Center, Branch of the National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia d Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia e Translational Technology Center, Moscow, Russia *e-mail: [email protected]
mother and the fetus [3, 4]. One of these classes of molecules can be microRNAs—short noncoding RNAs that regulate gene expression at the posttranscriptional level [5]. It is known that the miRNA sequence is not always canonical: miRNA isoforms that can be shorter or longer than the canonical form by seve
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