ArticleReproductive biology and endocrinology : RB&E2021
Down-regulation of the Sp1 transcription factor by an increase of microRNA-4497 in human placenta is associated with early recurrent miscarriage.
Article in Reproductive biology and endocrinology : RB&E, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 18 citations in OpenAlex.
- Identification and validation of cell senescence genes in recurrent spontaneous abortion via multiple bioinformatics algorithms.Scientific reports · 2025Article
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- Candidate Signature miRNAs from Secreted miRNAome of Human Lung Microvascular Endothelial Cells in Response to Different Oxygen Conditions: A Pilot Study.International journal of molecular sciences · 2024Article
- miR-526b-5p/c-Myc/Foxp1 participates in recurrent spontaneous abortion by regulating the proliferation, migration, and invasion of trophoblasts.Journal of assisted reproduction and genetics · 2023Article
- The Role of Placental Non-Coding RNAs in Adverse Pregnancy Outcomes.International journal of molecular sciences · 2023Review
- Micro-RNAs in Human Placenta: Tiny Molecules, Immense Power.Molecules (Basel, Switzerland) · 2022Review
- Review
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe pathophysiological mechanism of recurrent miscarriage (RM) is unclear. The goals of this study were to determine the role of microRNA-4497 overexpression in placental villus tissues in early RM; To identify the potential target mRNAs of miRNA-4497; And to investigate the microRNA-4497-mediated regulatory mechanisms in placental trophoblasts.
methodsBioinformatics analysis was performed to identify the candidate target genes of miRNA-4497. The protein expression of Sp1 transcription factor (SP1), chemokine (C-X-C motif) receptor 5 (CXCR5) and bone morphogenetic protein 8a (BMP8A) were determined in the villus tissues of the RM and normal groups by Western blotting and immunohistochemistry. Cultured 293T cells were co-transfected with the miRNA-4497 agomir or luciferase reporter vectors containing the wild-type or mutant 3'-UTRs of the target mRNAs to verify the regulatory role of miRNA-4497.
resultsBioinformatics analysis suggested that SP1, CXCR5 and BMP8A mRNAs are potential targets of miRNA-4497. The expression of SP1, CXCR5 and BMP8A proteins in the chorionic villus tissues of RM placentas were significantly decreased compared to those in the normal controls. Moreover, SP1 protein levels were inversely correlated with the levels of miRNA-4497 in the placentas of RM patients and normal controls. The expression of SP1 mRNA and protein were down-regulated in HTR-8/SVneo cells after forced overexpression of the miRNA-4497 agomir. The results of the co-transfection assay showed that mutation of the miRNA-4497-binding sites in the 3'-untranslated region (3'-UTR) of SP1 led to a recovery of luciferase activity upon overexpression of miRNA-4497, suggesting that SP1 could be a direct target of miRNA-4497.
conclusionsAn increased miRNA-4497 level in the placental villus tissues associated with recurrent miscarriage may down-regulate SP1 expression. The negative regulation of SP1 by miRNA-4497 may potentially contribute to the pathogenesis of recurrent miscarriage through promotion of trophoblast apoptosis. These findings provide novel information on the regulation of placental trophoblast apoptosis, and could be useful for the development of new therapeutic strategies for better management of recurrent miscarriage.
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