TY  - JOUR
AU  - Biró, Orsolya
AU  - Nagy, Bálint
AU  - Rigó, János
TI  - Identifying miRNA regulatory mechanisms in preeclampsia by systems biology approaches
JF  - HYPERTENSION IN PREGNANCY
J2  - HYPERT PREGN
VL  - 36
PY  - 2017
IS  - 1
SP  - 90
EP  - 99
PG  - 10
SN  - 1064-1955
DO  - 10.1080/10641955.2016.1239736
UR  - https://m2.mtmt.hu/api/publication/3152197
ID  - 3152197
AB  - BACKGROUND: Preeclampsia (PE) is the major cause of maternal and fetal morbidity and mortality, affecting 3-8% of all pregnancies around the globe. miRNAs are small, noncoding RNA molecules, which negatively regulate gene expression. Abnormally expressed miRNAs contribute to pregnancy complications such as PE. The aim of our study was to find possible regulatory mechanisms by system biology approaches, which are connected to the pathogenesis of PE. METHODS: We integrated publicly available miRNA and gene expression profiles and created a network from the significant miRNA-mRNA pairs with the help of MAGIA and Cytoscape softwares. Two subnetworks were expanded by adding protein-protein interactions. Differentially expressed miRNAs were identified for the evaluation of their regulatory effect. We analyzed the miRNAs and their targets using different bioinformatics tools and through literature research. RESULTS: Altogether, 52,603 miRNA-mRNA interactions were generated by the MAGIA web tool. The top 250 interactions were visualized and pairs with q < 0.0001 were analyzed, which included 85 nodes and 80 edges signalizing the connections between 52 regulated genes and 33 miRNAs. A total of 11 of the regulated genes are PE related and 9 of them were targeted by multiple miRNAs. A total of 8 miRNAs were associated with PE before, and 13 miRNAs regulated more than 1 mRNA. Hsa-mir-210 was the highest degree node in the network and its role in PE is well established. CONCLUSIONS: We identified several miRNA-mRNA regulatory mechanisms which may contribute to the pathogenesis of PE. Further investigations are needed to validate these miRNA-mRNA interactions and to enlighten the possibilities of developing potential therapeutic targets.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Biró, Orsolya
AU  - Alasztics, Bálint
AU  - Molvarec, Attila
AU  - Joó, József Gábor
AU  - Nagy, Bálint
AU  - Rigó, János
TI  - Various levels of circulating exosomal total-miRNA and miR-210 hypoxamiR in different forms of pregnancy hypertension
JF  - PREGNANCY HYPERTENSION
J2  - PREGNANCY HYPERTENS
VL  - 10
PY  - 2017
SP  - 207
EP  - 212
PG  - 6
SN  - 2210-7789
DO  - 10.1016/j.preghy.2017.09.002
UR  - https://m2.mtmt.hu/api/publication/3273020
ID  - 3273020
AB  - Introduction: Hypertension is a common complication during pregnancy, affecting 10% of pregnant women worldwide. Several microRNA (miRNA) were shown to be involved in hypertensive disorders of pregnancy. In preeclampsia (PE), placental dysfunction causes the enhanced release of extracellular vesicle-derived miRNAs. The hypoxia-sensitive hsa-mir-210 is the most common PE-associated miRNA, but its exosomal profile has not been investigated. Objectives: Our aims were to measure exosomal total-miRNA concentration and to perform expression analysis of circulating exosomal hsa-miR-210 in women affected by chronic hypertension (CHT) gestational hypertension (GHT) or PE. Materials and methods: We collected plasma samples from women with CHT, GHT, PE (moderate: mPE and severe: sPE) and from normotensive pregnancies. Exosomal miRNAs were extracted and miRNA concentration was measured. RT-PCR was carried out with hsa-miR-210-3p-specific primers and relative expression was calculated using the comparative Ct method. Results: The total-miRNA concentration was different in the disease subgroups, and was significantly higher in mPE and sPE compared to the other groups. We found a significant difference in the relative exosomal hsa-miR-210-3p expression between all hypertensive groups compared to the normotensive samples, but significant upregulation was only observed in case of mPE and sPE patients. Both the level of total-miRNA and hsa-miR-210 expression was higher in case of severe PE. Conclusions: The level of circulating exosomal total-miRNA and hsa-miR-210 was elevated in women with PE, and it was higher in the severe form. We showed that hsa-miR-210 is secreted via exosomes, which may have a role in the pathomechanism of the disease. © 2017 International Society for the Study of Hypertension in Pregnancy.
LA  - English
DB  - MTMT
ER  -