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 (bPOI) 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 bPOI 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 bPOI 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 bPOI individuals, suggesting that miR‐127‐5p could be a promising indicator for bPOI. 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.

中文翻译：

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MicroRNA-127-5p通过HMGB2基因在卵巢早衰中损害颗粒细胞的功能。

在早产的卵巢功能不全（POI）中已报道了不同的​​microRNA（miRNA）谱，但尚未明确指出它们在POI中的功能相关性。在这项研究中，miR‐127-5p和高迁移率第2号框（HMGB2通过微阵列在生化POI（bPOI）妇女的颗粒细胞（GC）中观察到，并通过定量逆转录聚合酶链反应进一步证实。永生化的人类颗粒细胞系和小鼠原代卵巢GC用于功能验证。建立了原位小鼠模型以检查miR‐127‐5p在体内的作用。最后，在bPOI妇女的血浆中测量了miR-1275p的表达。进行接收器工作特征曲线分析以确定miR‐127-5p对卵巢储备的指示作用。结果表明，在bPOI患者的GC中鉴定出miR‐127-5p的上调。它通过靶向HMGB2抑制GC增殖并削弱DNA损伤修复能力。，这在同一病例组的GC中显着下调。证实miR‐127-5p可通过HMGB2减弱小鼠体内卵巢的DNA修复能力。有趣的是，在bPOI个体血浆中也检测到miR‐127-5p的过度表达，这表明miR‐127-5p可能是bPOI的有前途的指标。两者合计，我们的结果发现miR‐127-5p对GC功能的有害影响及其在POI过程中的预测价值。靶基因HMGB2可以被认为是POI的新候选者。这项研究强调了DNA修复能力对卵巢功能的重要性，并阐明了POI致病性的表观遗传机制。