miR-210 targets iron-sulfur cluster scaffold homologue in human trophoblast cell lines: siderosis of interstitial trophoblasts as a novel pathology of preterm preeclampsia and small-for-gestational-age pregnancies.

Abstract

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.

• Authors: Deug-Chan Lee, Roberto Romero, Jung-Sun Kim, Adi L Tarca, Daniel Montenegro, Beth L Pineles, Ernest Kim, JoonHo Lee, Sun Young Kim, Sorin Draghici, Pooja Mittal, Juan Pedro Kusanovic, Tinnakorn Chaiworapongsa, Sonia S Hassan, Chong Jai Kim
• Journal: The American journal of pathology (Am J Pathol) Vol. 179 Issue 2 Pg. 590-602 (Aug 2011) ISSN: 1525-2191 [Electronic] United States
• PMID: 21801864 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• 3' Untranslated Regions
• ISCU protein, human
• Iron-Sulfur Proteins
• MIRN210 microRNA, human
• MicroRNAs

Topics

• 3' Untranslated Regions
• Adolescent
• Adult
• Cell Line
• Cell Line, Tumor
• Choriocarcinoma (metabolism)
• Female
• Humans
• Hypoxia
• In Situ Hybridization
• Infant, Newborn
• Infant, Small for Gestational Age
• Iron-Sulfur Proteins (metabolism)
• MicroRNAs (genetics)
• Middle Aged
• Placenta (metabolism)
• Pre-Eclampsia (metabolism)
• Pregnancy
• RNA Interference
• Siderosis (pathology)
• Trophoblasts (metabolism)