Plasma-derived exosomal miRNA profiles reveal potential epigenetic pathogenesis of premature ovarian failure.

IF 3.8 2区生物学 Q2 GENETICS & HEREDITY

Human Genetics Pub Date : 2024-10-01 Epub Date: 2023-12-06 DOI:10.1007/s00439-023-02618-1

Jiaqiong Lin, Zhihong Wu, Yingchun Zheng, Zongrui Shen, Zhongzhi Gan, Shunfei Ma, Yanhui Liu, Fu Xiong

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引用次数: 0

Abstract

The role of plasma-derived exosomal miRNA in premature ovarian failure (POF) remains unclear. This study aimed to investigate the epigenetic pathogenesis of POF through exosomal miRNA sequencing. Exosomes were isolated and characterized from six POF patients and four healthy individuals using nanoparticle tracking analysis, transmission electron microscopy and western blot analysis. Exosomal miRNA sequencing was performed to identify differentially expressed miRNAs with |fold change| greater than 1.5 and p value less than 0.05. Bioinformatics analysis in GSE39501 dataset and our sequencing data was conducted to investigate underlying mechanisms of POF. The functional role of hsa-miR-19b-3p was assessed using CCK8, western blot, flow cytometry and fluorescence staining. The regulatory effect of hsa-miR-19b-3p on BMPR2 was investigated through miRNA transfection, qPCR analysis, and luciferase reporter assay. Statistical significance was determined using t-tests and one-way ANOVA (p < 0.05). Exosomal miRNA sequencing revealed 18 dysregulated miRNAs in POF patients compared to healthy controls. Functional enrichment analysis demonstrated their involvement in cell growth, oocyte meiosis and PI3K-Akt signaling pathways. Moreover, the constructed miRNA-mRNA network unveiled potential regulatory mechanisms underlying POF, particularly implicating hsa-miR-19b-3p in the regulation of BMPR2. In vitro assays conducted on KGN cells confirmed that hsa-miR-19b-3p promoted apoptosis, as evidenced by reduced cell viability, decayed mitochondrial membrane potential and increased apoptotic rate, thereby supporting its role in POF. Notably, hsa-miR-19b-3p was found to significantly downregulate BMPR2 expression via targeting its 3'UTR, while co-expression analysis revealed strong associations between BMPR2 and POF-related processes. This study sheds light on the epigenetic pathogenesis of POF by investigating exosomal miRNA profiles. Particularly, hsa-miR-19b-3p emerged as a potential regulator of BMPR2 and demonstrated its functional significance in POF through modulation of apoptosis.

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血浆来源的外泌体 miRNA 图谱揭示了卵巢早衰的潜在表观遗传发病机制。

血浆来源的外泌体miRNA在卵巢早衰（POF）中的作用仍不清楚。本研究旨在通过外泌体miRNA测序研究POF的表观遗传发病机制。利用纳米粒子追踪分析、透射电子显微镜和免疫印迹分析，从6名POF患者和4名健康人体内分离并鉴定了外泌体。外泌体miRNA测序的目的是鉴定|fold change|大于1.5且p值小于0.05的差异表达miRNA。对 GSE39501 数据集和我们的测序数据进行了生物信息学分析，以研究 POF 的潜在机制。利用 CCK8、Western 印迹、流式细胞术和荧光染色评估了 hsa-miR-19b-3p 的功能作用。通过 miRNA 转染、qPCR 分析和荧光素酶报告实验研究了 hsa-miR-19b-3p 对 BMPR2 的调控作用。统计意义采用 t 检验和单因素方差分析（p

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来源期刊

Human Genetics 生物-遗传学

CiteScore

10.80

自引率

3.80%

发文量

审稿时长

1 months

期刊介绍： Human Genetics is a monthly journal publishing original and timely articles on all aspects of human genetics. The Journal particularly welcomes articles in the areas of Behavioral genetics, Bioinformatics, Cancer genetics and genomics, Cytogenetics, Developmental genetics, Disease association studies, Dysmorphology, ELSI (ethical, legal and social issues), Evolutionary genetics, Gene expression, Gene structure and organization, Genetics of complex diseases and epistatic interactions, Genetic epidemiology, Genome biology, Genome structure and organization, Genotype-phenotype relationships, Human Genomics, Immunogenetics and genomics, Linkage analysis and genetic mapping, Methods in Statistical Genetics, Molecular diagnostics, Mutation detection and analysis, Neurogenetics, Physical mapping and Population Genetics. Articles reporting animal models relevant to human biology or disease are also welcome. Preference will be given to those articles which address clinically relevant questions or which provide new insights into human biology. Unless reporting entirely novel and unusual aspects of a topic, clinical case reports, cytogenetic case reports, papers on descriptive population genetics, articles dealing with the frequency of polymorphisms or additional mutations within genes in which numerous lesions have already been described, and papers that report meta-analyses of previously published datasets will normally not be accepted. The Journal typically will not consider for publication manuscripts that report merely the isolation, map position, structure, and tissue expression profile of a gene of unknown function unless the gene is of particular interest or is a candidate gene involved in a human trait or disorder.