Upregulation of HIF1A /miR-210 and downregulation of miR-383 in EOPE, IUGR, and EOPE/IUGR: Integrative bioinformatics insights into miR-383 targets
Placenta, cilt.182, ss.315-329, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 182
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.placenta.2026.07.003
- Dergi Adı: Placenta
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CINAHL, EMBASE, MEDLINE
- Sayfa Sayıları: ss.315-329
- Anahtar Kelimeler: HIF1A, Hypoxia, IUGR, miR-210, miR-383, Preeclampsia
- Sivas Cumhuriyet Üniversitesi Adresli: Evet
Özet
Introduction: Intrauterine growth restriction (IUGR), early-onset preeclampsia (EOPE), and EOPE/IUGR are characterized by reduced trophoblast invasion, hypoxia, and impaired angiogenesis. While hypoxia-related HIF1A and miR-210 have been extensively studied, the role of miR-383 remains poorly understood. This study aimed to investigate the expression levels of HIF1A, miR-210, and miR-383, and to evaluate miR-383 target genes through bioinformatics analyses. Methods: The study included 22 EOPE, 20 IUGR, 18 EOPE/IUGR, and 30 healthy pregnancies. Expression of HIF1A, miR-210, and miR-383 was measured in maternal blood, cord blood, and placental tissues using RT-qPCR. For miR-383 target analysis, differentially expressed genes (DEGs) from GSE114691 RNA-seq data were intersected with predicted targets from TargetScan 7.1. Commonly up- and downregulated miR-383 targets were subjected to functional analyses using DAVID, Enrichr, STRING, and GeneMANIA. Results: Compared with controls, the expression of HIF1A and miR-210 was significantly increased in all samples from IUGR, EOPE/IUGR, and EOPE cases. Conversely, miR-383 was consistently downregulated in placental tissues: IUGR fetal tissue (0.42-fold, p < 0.0001), EOPE fetal tissue (0.50-fold, p < 0.0001), and EOPE/IUGR maternal tissue (0.11-fold, p < 0.0001). Bioinformatics analysis of GSE114691 revealed that 23 miR-383 targets were commonly upregulated and 27 were commonly downregulated across IUGR, EOPE, and EOPE/IUGR groups. Functional analyses and literature integration identified upregulated EPAS1, IRF1, and GLIS3, and downregulated RUNX1 and ACVR1B as core genes linking miR-383 dysregulation to placental dysfunction. According to the validation analyses, the increase in EPAS1 and GLIS3 expressions was found to be statistically significant, whereas RUNX1 expression levels were determined to be decreased in fetal tissue. Conclusion: HIF1A and miR-210 are upregulated, while miR-383 is downregulated in placental dysfunction. Its targets are associated with hypoxia, trophoblast invasion, proliferation, and angiogenesis.