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首页> 外文期刊>Journal of cellular physiology. >MicroRNA-127-5p impairs function of granulosa cells via HMGB2 gene in premature ovarian insufficiency
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MicroRNA-127-5p impairs function of granulosa cells via HMGB2 gene in premature ovarian insufficiency

机译：微rna - 127 - 5 - p削弱颗粒的函数细胞通过HMGB2基因在卵巢功能机能不全

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摘要

Distinct microRNA (miRNA) profiles have been reported in premature ovarian insufficiency (POI), but their functional relevance in POI is not yet clearly stated. In this study, aberrant expressions of miR-127-5p and high mobility group box 2 (HMGB2) were observed by microarrays in granulosa cells (GCs) from biochemical POI (bPOl) women and further confirmed by a quantitative reverse-transcription polymerase chain reaction. Immortalized human granulosa cell line and mouse primary ovarian GCs were used for functional validation. Orthotopic mouse model was established to examine the role of miR-127-5p in vivo. Finally, the expression of miR-127-5p was measured in the plasma of bPOl women. The receiver operating characteristic curve analysis was performed to determine the indicative role of miR-127-5p for ovarian reserve. Results showed the upregulation of miR-127-5p was identified in GCs from bPOl patients. It inhibited GCs proliferation and impaired DNA damage repair capacity through targeting HMGB2, which was significantly downregulated in GCs from the same cohort of cases. miR-127-5p was confirmed to attenuate DNA repair capability via HMGB2 in mouse ovary in vivo. Intriguingly, the upexpression of miR-127-5p was also detected in plasma of bPOl individuals, suggesting that miR-127-5p could be a promising indicator for bPOl. Taken together, our results discovered the deleterious effects of miR-127-5p on GCs function and its predictive value in POI process. The target gene HMGB2 could be considered as a new candidate for POI. This study highlights the importance of DNA repair capacity for ovarian function and sheds light on the epigenetic mechanism in the pathogenicity of POI.
机译：不同的微rna (microRNA)配置文件在卵巢功能不足(POI),但是它们的功能相关性在POI没有明确表示。mir - 127 - 5 - p的表达和高机动组箱2 (HMGB2)所观察到的微阵列颗粒细胞(GCs)生化POI (bPOl)女性,进一步证实了量化逆转录聚合酶链反应。人类颗粒细胞永生化和鼠标原发性卵巢GCs用于功能验证。建立检查mir - 127 - 5 - p的角色vivo测量了等离子体的bPOl女性。接受者操作特征曲线分析确定执行的指示性作用mir - 127 - 5 - p卵巢储备。mir - 127 - 5 - p的upregulation被确认GCs bPOl病人。核扩散和DNA损伤修复受损通过针对HMGB2能力,这是大幅下调的GCs相同群情况。通过HMGB2在DNA修复能力减弱老鼠体内卵巢。上调mir - 127 - 5 - p也被检测到等离子体bPOl个人,这表明mir - 127 - 5 - p可能是一个有前途的指标bPOl。有害的影响mir - 127 - 5 - p对GCs功能及其在POI预测价值的过程。目标基因HMGB2可以被认为是一个新的POI候选人。DNA修复卵巢的能力的重要性函数,揭示了表观遗传POI的致病性机制。

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