MiR-26a-5p/EZH2 Mediates Wnt2 Promoter Methylation to Regulate Trophoblast Dysfunction.

IF 1.6 4区医学 Q4 BIOCHEMICAL RESEARCH METHODS

Combinatorial chemistry & high throughput screening Pub Date : 2025-04-24 DOI:10.2174/0113862073360368250404104831

Xiaoyu Zhou, Shiqi Wei, Ning Yu, Yufang Liu

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引用次数: 0

Abstract

Background: Preeclampsia (PE) is a common complication of pregnancy, with a concomitant incidence rate of up to 10% among pregnant women worldwide.

Methods: In the current research, we explored the role and mechanism of miR-26a-5p in trophoblast function using CCK-8, colony formation assay, and flow cytometry. The interaction between miR-26a-5p and EZH2 was analyzed using a luciferase reporter assay. Methylationspecific PCR was performed to detect the methylation level of Wnt2 in HTR8 cells.

Results: Wnt2 and miR-26a-5p promoted the proliferation and inhibited the apoptosis in trophoblasts (P<0.05). The secretion of inflammatory cytokines was suppressed by Wnt2 and miR-26a- 5p (P<0.05). EZH2 was identified as a regulatory target of miR-26a-5p using HTR8 cells and bioinformatic tools. miR-26a-5p inhibited expression through direct binding to EZH2. Importantly, miR-26a-5p mediated DNA methylation of Wnt2 to regulate Wnt2 expression in HTR8 cells.

Conclusion: It was found that miR-26a-5p increased the expression of Wnt2 by downregulating EZH2. Moreover, miR-26a-5p/EZH2/Wnt2 promoted the proliferation and inhibited the inflammation and apoptosis in trophoblasts. This research provides insight into the role of miR-26a- 5p/EZH2/Wnt2 as a novel indicator for the prevention and treatment of PE.

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MiR-26a-5p/EZH2介导Wnt2启动子甲基化调节滋养细胞功能障碍

背景：先兆子痫（PE）是一种常见的妊娠并发症，在全世界孕妇中发病率高达10%。方法：在当前的研究中，我们通过CCK-8、集落形成实验和流式细胞术探讨了miR-26a-5p在滋养细胞功能中的作用和机制。使用荧光素酶报告基因检测分析miR-26a-5p和EZH2之间的相互作用。采用甲基化特异性PCR检测HTR8细胞中Wnt2的甲基化水平。结果：Wnt2和miR-26a-5p促进滋养细胞增殖，抑制细胞凋亡(p)结论：发现miR-26a-5p通过下调EZH2上调Wnt2的表达。此外，miR-26a-5p/EZH2/Wnt2促进滋养细胞增殖，抑制炎症和凋亡。本研究揭示了miR-26a- 5p/EZH2/Wnt2作为PE预防和治疗的新指标的作用。

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来源期刊

Combinatorial chemistry & high throughput screening 化学-生化研究方法

CiteScore

3.10

自引率

5.60%

发文量

327

审稿时长

7.5 months

期刊介绍： Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal: Target identification and validation Assay design, development, miniaturization and comparison High throughput/high content/in silico screening and associated technologies Label-free detection technologies and applications Stem cell technologies Biomarkers ADMET/PK/PD methodologies and screening Probe discovery and development, hit to lead optimization Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) Chemical library design and chemical diversity Chemo/bio-informatics, data mining Compound management Pharmacognosy Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products) Natural Product Analytical Studies Bipharmaceutical studies of Natural products Drug repurposing Data management and statistical analysis Laboratory automation, robotics, microfluidics, signal detection technologies Current & Future Institutional Research Profile Technology transfer, legal and licensing issues Patents.