WNT5A, β‑catenin and SUFU expression patterns, and the significance of microRNA deregulation in placentas with intrauterine growth restriction
| Autor: | Ida Sola, Valentina Karin‑Kujundzic, Frane Paic, Lada Lijovic, Mislav Glibo, Nikola Serman, Tihana Duic, Anita Skrtic, Krunoslav Kuna, Semir Vranic, Ljiljana Serman |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Cancer Research
beta Catenin / genetics intrauterine growth restriction placenta Repressor Proteins / genetics Fetal Growth Retardation / genetics Hh signaling pathway Biochemistry Wnt signaling pathway Pregnancy Genetics Placenta / pathology beta Catenin / metabolism Humans Molecular Biology Placenta / metabolism Wnt-5a Protein / metabolism DNA methylation Repressor Proteins / metabolism Endothelial Cells / metabolism Infant Newborn suppressor of fused Fetal Growth Retardation / pathology MicroRNAs / metabolism MicroRNAs / genetics Oncology Intrauterine growth restriction Placenta WNT5A β‑catenin Suppressor of fused microRNA 214 microRNA 378 Molecular Medicine Female Wnt-5a Protein / genetics |
| DOI: | 10.3892/mmr.2022.12914 |
| Popis: | Placental insufficiency is a common cause of intrauterine growth restriction (IUGR). It affects ~10% of pregnancies and increases fetal and neonatal morbidity and mortality. Although Wnt and Hh pathways are crucial for embryonic development and placentation, their role in the pathology of IUGR is still not sufficiently explored. The present study analyzed the expression of positive regulators of the Wnt pathway, WNT5A and β‑catenin, and the expression of the Hh pathway negative regulator suppressor of fused (SUFU). Immunohistochemical and reverse transcription‑quantitative PCR (RT‑qPCR) assays were performed on 34 IUGR and 18 placental tissue samples from physiologic singleton‑term pregnancies. Epigenetic mechanisms of SUFU gene regulation were also investigated by methylation‑specific PCR analysis of its promoter and RT‑qPCR analysis of miR‑214‑3p and miR‑378a‑5p expression. WNT5A protein expression was higher in endothelial cells of placental villi from IUGR compared with control tissues. That was also the case for β‑catenin protein expression in trophoblasts and endothelial cells and SUFU protein expression in trophoblasts from IUGR placentas. The SUFU gene promoter remained unmethylated in all tissue samples, while miR‑214‑3p and miR‑378a‑5p were downregulated in IUGR. The present results suggested altered Wnt and Hh signaling in IUGR. DNA methylation did not appear to be a mechanism of SUFU regulation in the pathogenesis of IUGR, but its expression could be regulated by miRNA targeting. |
| Databáze: | OpenAIRE |
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