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miR-515-5p suppresses trophoblast cell invasion and proliferation through XIAP regulation in preeclampsia
Misa Nunode1, Masami Hayashi1, Yoko Nagayasu1
1Department of Obstetrics and Gynecology, Osaka Medical and Pharmaceutical University, 2-7 Daigakumachi, Takatsuki, Osaka, 569-8686, Japan.
Abstract:
MicroRNAs (miRNAs) are non-coding small RNA molecules that can be secreted into the circulation and which exist in remarkably stable forms. Circulating miRNAs regulate numerous biological process and are aberrantly expressed in pathological conditions. Differentially expressed circulating miRNAs have received attention as potential biomarkers for many diseases. In this study, we revealed that miR-515-5p was significantly upregulated in maternal serum from preeclampsia patients in comparison to normal pregnant women. Bioinformatics prediction and a dual-luciferase reporter gene assay revealed that miR-515-5p directly targets the X-linked inhibitor of apoptosis protein (XIAP) 3'-untranslated region. In addition, the overexpression of miR-515-5p inhibited the proliferation and invasion of HTR-8/SVneo trophoblast cells. The decreased XIAP expression and reduced epithelial-mesenchymal transition (EMT) were observed in the preeclamptic placenta. Collectively, miR-515-5p may play critical roles in the pathogenesis of preeclampsia through suppression of XIAP, and serum miR-515-5p may act as a potential biomarker for preeclampsia.
Insights
Serum miR-515-5p is upregulated in preeclampsia and may serve as a diagnostic biomarker. This microRNA targets XIAP, inhibiting trophoblast cell proliferation and invasion, suggesting a role in preeclampsia pathogenesis.
Area of Science:
- Molecular Biology
- Biochemistry
- Reproductive Medicine
Background:
- MicroRNAs (miRNAs) are stable, secreted small non-coding RNAs involved in biological regulation.
- Aberrant miRNA expression is linked to various pathological conditions, making them potential disease biomarkers.
- Preeclampsia is a serious pregnancy complication with complex underlying molecular mechanisms.
Purpose of the Study:
- To investigate the role of miR-515-5p in preeclampsia pathogenesis.
- To identify miR-515-5p as a potential circulating biomarker for preeclampsia.
- To elucidate the molecular targets and functions of miR-515-5p in trophoblast cells.
Main Methods:
- Quantification of serum miR-515-5p levels in preeclampsia patients and normal pregnant women.
- Bioinformatics prediction and dual-luciferase reporter assays to identify miR-515-5p targets.
- In vitro studies using HTR-8/SVneo trophoblast cells to assess the functional impact of miR-515-5p overexpression on proliferation, invasion, and XIAP expression.
- Analysis of XIAP expression and epithelial-mesenchymal transition (EMT) markers in placental tissues.
Main Results:
- miR-515-5p was significantly upregulated in the serum of preeclampsia patients compared to controls.
- miR-515-5p was confirmed to directly target the 3'-untranslated region of the X-linked inhibitor of apoptosis protein (XIAP).
- Overexpression of miR-515-5p suppressed trophoblast cell proliferation and invasion.
- Decreased XIAP expression and reduced EMT were observed in preeclamptic placentas.
Conclusions:
- miR-515-5p plays a crucial role in preeclampsia pathogenesis by suppressing XIAP.
- The miR-515-5p/XIAP axis influences trophoblast cell behavior and EMT.
- Circulating miR-515-5p holds promise as a non-invasive biomarker for preeclampsia diagnosis.
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