miR-210 Targets Iron-Sulfur Cluster Scaffold Homologue in Human Trophoblast Cell Lines
Open accessAbstract
This study was performed to assess the biological significance of miR-210 in preeclampsia and small-for-gestational-age (SGA) pregnancies. Placental miR-210 expression was evaluated by quantitative RT-PCR (RT-qPCR) in the following groups: i) appropriate-for-gestational-age pregnancies (n = 72), ii) preeclampsia (n = 52), iii) SGA (n = 66), and iv)preeclampsia with SGA (n = 31). The effects of hypoxia (1% O(2)) on miR-210 and iron-sulfur cluster scaffold homologue (ISCU) expressions and miR-210 binding to ISCU 3' UTR were examined in Swan 71 and BeWo cell lines. Perls' reaction (n = 229) and electron microscopy (n = 3) were conducted to verify siderosis of trophoblasts. miR-210 expression was increased in preeclampsia and SGA cases and was decreased with birth weight and gestational age. In both cell lines, miR-210 was induced by hypoxia, whereas ISCU expression was decreased. The luciferase assay confirmed miR-210 binding to ISCU mRNA 3' UTR. RNA interference knockdown of ISCU expression in Swan 71, but not in BeWo, cells resulted in autophagosomal and siderosomal iron accumulation and a fourfold decrease of Matrigel invasion (P = 0.004). Placental ISCU expression was decreased in preeclampsia (P = 0.002) and SGA (P = 0.002) cases. Furthermore, hemosiderin-laden trophoblasts were more frequent in the placental bed of preterm preeclampsia and/or SGA births than in control cases (48.7% versus 17.9%; P = 0.004). Siderosis of interstitial trophoblasts is a novel pathological feature of preeclampsia and SGA. The findings herein suggest that ISCU down-regulation by miR-210 perturbing trophoblast iron metabolism is associated with defective placentation.
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miR-210 was induced by hypoxia, and RNA interference knockdown resulted in autophagosomal and siderosomal iron accumulation, implicating siderosis or interstitial trophoblasts as mechanisms in preeclampsia and SGA.
“Additionally, it was demonstrated that miR-210 was induced by hypoxia, and RNA interference knockdown resulted in autophagosomal and siderosomal iron accumulation, implicating siderosis or interstitial trophoblasts as mechanisms in preeclampsia and SGA(206)”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [206]
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- Authors
- Lee, D.-C., Romero, R., Kim, J.-S., Tarca, A. L., Montenegro, D., Pineles, B. L., Kim, E., Lee, J., Kim, S. Y., Draghici, S., Mittal, P., Kusanovic, J. P., Chaiworapongsa, T., Hassan, S. S., & Kim, C. J.
- Affiliations
- National Institutes of Health (US)
- Samsung Medical Center (KR)
- Corresponding author
- Romero, Roberto
- Kim, Chong Jai
- ORCID
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2011-08
- Volume
- 179
- Issue
- 2
- Pages
- 590-602
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC3160082
- OpenAlex
- W73897435
- Cited by
- 135
- References
- 72
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 2 · 2023: 7 · 2022: 11 · 2021: 11 · 2020: 7 · 2019: 14 · 2018: 13 · 2017: 16 · 2016: 10 · 2015: 10 · 2014: 7 · 2013: 11 · 2012: 6
- FWCI
- 10.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- National Institutes of Health
- U.S. Department of Health and Human Services
- 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-210, IscU, preeclampsia, small for gestational age, hypoxia, trophoblast invasion, autophagy, hemosiderin, placental microRNAs, placentation
- MeSH terms
- Adolescent, Adult, Hypoxia, Cell Line, Choriocarcinoma, Female, Humans, Infant, Newborn, Infant, Small for Gestational Age, Iron-Sulfur Proteins, Middle Aged, Placenta, Pre-Eclampsia, Pregnancy, Siderosis, Trophoblasts, In Situ Hybridization, 3' Untranslated Regions, RNA Interference, MicroRNAs, Cell Line, Tumor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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