ArticleReproductive biology and endocrinology : RB&E2021
MicroRNA-3935 promotes human trophoblast cell epithelial-mesenchymal transition through tumor necrosis factor receptor-associated factor 6/regulator of G protein signaling 2 axis.
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 16 papers.
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16 citing papers in PubMed, 20 citations in OpenAlex.
- The role of miRNA in modulating oxidative stress in preeclampsia: current knowledge.RNA biology · 2026Review
- New Frontiers in the Pathophysiology of Hypertensive Pregnancy Disorders: A Systematic Review of Molecular Insights into Preeclampsia.Current issues in molecular biology · 2026Review
- Review
- Trophoblast Function in Preeclampsia: Decoding the Mechanistic Roles of Coding and Non-Coding Genes.International journal of molecular sciences · 2025Review
- Potential function of miRNA as a diagnostic biomarker for human ovarian cancer.Discover oncology · 2025Review
- MicroRNAs in Preeclampsia: An Overview of Biomarkers and Potential Therapeutic Targets.International journal of molecular sciences · 2025Review
- Regulation of placental development and function by ubiquitination.Molecular medicine (Cambridge, Mass.) · 2025Review
- Gastrodin Protects Neuronal Cells Against Oxidative Stress Through miRNA-125b-5p/Mamdc2 Axis.Neuromolecular medicine · 2025Article
- Exosome-delivered miR-410-3p reverses epithelial-mesenchymal transition, migration and invasion of trophoblasts in spontaneous abortion.Journal of cellular and molecular medicine · 2024Article
- GPR137 inactivates Hippo signaling to promote gastric cancer cell malignancy.Biology direct · 2024Article
- RGS2 and female common diseases: a guard of women's health.Journal of translational medicine · 2023Review
- Yap1-Usp14 Axis Inhibits Neuronal Mitophagy During Neonatal Hypoxia-Ischemia Encephalopathy by Regulation of Beclin-1 Ubiquitination in Mouse.Molecular neurobiology · 2023Article
- RGS proteins and their roles in cancer: friend or foe?Cancer cell international · 2023Review
- RGS2 promotes estradiol biosynthesis by trophoblasts during human pregnancy.Experimental & molecular medicine · 2023Article
- Micro-RNAs in Human Placenta: Tiny Molecules, Immense Power.Molecules (Basel, Switzerland) · 2022Review
- Tianma Gouteng Decoction Exerts Pregnancy-Protective Effects Against PreeclampsiaFrontiers in pharmacology · 2022Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundInsufficient migration and invasion during trophoblast epithelial-mesenchymal transition (EMT) results in the occurrence and development of preeclampsia (PE), and our previous study has screened 52 miRNAs, whose expression levels are altered in the placental samples from PE patients, compared with the normal group. Among those, miR-3935 is one of the miRNAs being most significantly down-regulated, indicating its involvement in PE. However, the exact effect and molecular mechanisms remain unknown.
methodsIn the present study, we investigate the roles and underlying mechanisms of miR-3935 in trophoblast EMT by use of the human extra-villous trophoblast cell line HTR-8/SVneo as well as human placental tissues and maternal blood samples obtained from 15 women with normal pregnancies and 15 women with PE. Experimental methods include transfection, quantitative reverse transcription-PCR (qRT-PCR), western blot, immunofluorescence staining, dual-luciferase assays, in vitro invasion and migration assays, RNA-Seq analysis, bisulfite sequencing and immunohistochemistry staining.
resultsMiR-3935 expression is significantly decreased in both placentas and peripheral blood specimens of PE, and functionally, miR-3935 promotes EMT of trophoblast cells. Mechanistically, TRAF6 is identified to be a direct target of miR-3935 and TRAF6 exerts its negative effect on EMT of trophoblast cells by inhibition of RGS2, which down-regulates the methylation status of promoter of CDH1 gene that encodes E-Cadherin protein through induction of ALKBH1, resulting in increase of E-Cadherin and subsequently insufficient trophoblast EMT.
conclusionsTogether these results uncover a hitherto uncharacterized role of miR-3935/TRAF6/RGS2 axis in the function of human trophoblasts, which may pinpoint the molecular pathogenesis of PE and may be a prognostic biomarker and therapeutic target for such obstetrical diseases as PE.
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