miR-34a expression, epigenetic regulation, and function in human placental diseases
Open accessAbstract
Preeclampsia (PE) is the major pregnancy-induced hypertensive disorder responsible for maternal and fetal morbidity and mortality that can be associated with intrauterine growth restriction (IUGR). PE and IUGR are thought to be due to a placental defect, occurring early during pregnancy. Several placental microRNAs (miRNAs) have been shown to be deregulated in the context of placental diseases and could thus play a role in the pathophysiology of PE. Here, we show that pri-miR-34a is overexpressed in preeclamptic placentas and that its placental expression is much higher during the first trimester of pregnancy than at term, suggesting a possible developmental role. We explored pri-miR-34a regulation and showed that P53, a known activator of miR-34a, is reduced in all pathological placentas and that hypoxia can induce pri-miR-34a expression in JEG-3 cells. We also studied the methylation status of the miR-34a promoter and revealed hypomethylation in all preeclamptic placentas (associated or not with IUGR), whereas hypoxia induced a hypermethylation in JEG-3 cells at 72 h. Despite the overexpression of pri-miR-34a in preeclampsia, there was a striking decrease of the mature miR-34a in this condition, suggesting preeclampsia-driven alteration of pri-miR-34a maturation. SERPINA3, a protease inhibitor involved in placental diseases, is elevated in IUGR and PE. We show here that miR-34a overexpression in JEG-3 downregulates SERPINA3. The low level of mature miR-34a could thus be an important mechanism contributing to SERPINA3 upregulation in placental diseases. Overall, our results support a role for miR-34a in the pathophysiology of preeclampsia, through deregulation of the pri-miRNA expression and its altered maturation.
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Micro-RNAs identified as being differentially expressed under hypoxia include miR-93, miR-205, miR-224, MiR-335, MiR-424, miR-451, miR-491 and mIR-34a.
“Many of these Other micro-RNAs identified as being differentially expressed under hypoxia include miR-93, miR-205, miR-224, MiR-335, MiR-424, miR-451 and miR-491 (396, 397), and mIR-34a (154), but little is known regarding their functional significance at present.”
From Placental Origins of Chronic Disease (2016) · cites this paper as [154]
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Prediction of Preeclampsia-Bench to Bedside
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HIF1α/miR-146α/TRAF6/NF-κB axis modulates hepatic iron overload-induced inflammation
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A mikro-RNS-ek patogenetikai szerepe és expressziós mintázata praeeclampsiában
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- Authors
- Doridot, L., Houry, D., Gaillard, H., Chelbi, S. T., Barbaux, S., & Vaiman, D.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Vaiman, Daniel
- Venue
- Epigenetics
- Publisher
- Informa UK Limited
- Published
- 2013-09-30
- Volume
- 9
- Issue
- 1
- Pages
- 142-151
- ISSN
- 1559-2294 (ISSN-L)
- 1559-2308
- PMC
- PMC3928177
- OpenAlex
- W2020698835
- Cited by
- 65
- References
- 40
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 7 · 2022: 8 · 2021: 7 · 2020: 2 · 2019: 5 · 2018: 4 · 2017: 5 · 2016: 8 · 2015: 9 · 2014: 4 · 2013: 1
- FWCI
- 8.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Epigenetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- miR-34a, preeclampsia, fetal growth restriction, placental disease, DNA methylation, hypoxia, p53, alpha-1-antichymotrypsin, protease inhibitors, JEG-3 cells, epigenetic regulation
- MeSH terms
- Hypoxia, Choriocarcinoma, Female, Humans, Placenta Diseases, Pre-Eclampsia, Pregnancy, Promoter Regions, Genetic, Uterine Neoplasms, Serpins, Tumor Suppressor Protein p53, DNA Methylation, MicroRNAs, Epigenesis, Genetic, Cell Line, Tumor
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