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 - Xu, H AU - Han, Y AU - Lou, J AU - Zhang, H AU - Zhao, Y AU - Győrffy, Balázs AU - Li, R TI - PDGFRA, HSD17B4 and HMGB2 are potential therapeutic targets in polycystic ovarian syndrome and breast cancer JF - ONCOTARGET J2 - ONCOTARGET VL - 8 PY - 2017 IS - 41 SP - 69520 EP - 69526 PG - 7 SN - 1949-2553 DO - 10.18632/oncotarget.17846 UR - https://m2.mtmt.hu/api/publication/3238399 ID - 3238399 AB - To explore the key genes associated with both PCOS and breast cancer, we overlapped the synchronously differently expressed genes in two obese insulin-resistant GEO datasets in muscle tissue and genes exert essential roles in breast cancer prognosis together base on the following reasons: (1) Androgens excess is believed to contribute to the onset of both PCOS and breast cancer. (2) PCOS is usually complicated with metabolic symptoms, such as obesity and insulin-resistance. (3) Muscle is the main place where energy metabolism and material metabolism take place. Consequently, 53 genes were found, functionally enriched in pathways such as pyruvate metabolism, muscle system process and development of primary male sexual characteristics etc. We further lay our eyes on genes correlated with male sexual characteristics, which may be involved in the onset of both PCOS and breast cancer. Three genes were indicated to be associated with this process, including hydroxysteroid (17-beta) dehydrogenase 4/HSD17B4, platelet-derived growth factor receptor, alpha polypeptide/PDGFRA and high-mobility group box 2/HMGB2. Gene-drug interaction network about the three genes were then constructed. Drugs or chemicals that contribute to correcting the disorder of lipid metabolism were detected to restore the abnormal expression of the three genes in PCOS, such as simvastatin, bezafibrate, fenofibrate et al, which provide further choices for managing patients with PCOS. LA - English DB - MTMT ER -