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MicroRNA-379-5p is associated with biochemical premature ovarian insufficiency through PARP1 and XRCC6

机译:MicroRNA-379-5P通过PARP1和XRC6与生化过早卵巢功能不全相关

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Premature ovarian insufficiency (POI) imposes great challenges on women’s fertility and lifelong health. POI is highly heterogeneous and encompasses occult, biochemical, and overt stages. MicroRNAs (miRNAs) are negative regulators of gene expression, whose roles in physiology and diseases like cancers and neurological disorders have been recognized, but little is known about the miRNAs profile and functional relevance in biochemical POI (bPOI). In this study, the expression of miRNAs and mRNAs in granulosa cells (GCs) of bPOI women was determined by two microarrays, respectively. MiR-379-5p, PARP1, and XRCC6 were differentially expressed in GCs of bPOI as revealed by microarrays. Subsequently, functional studies demonstrated that miR-379-5p overexpression inhibited granulosa cell proliferation and attenuated DNA repair efficiency. Furthermore, both PARP1 and XRCC6 showed lower levels in GCs from patients with bPOI and were identified as executives of miR-379-5p. Therefore, our data first uncovered potentially pathogenic miR-379-5p and two novel targets PARP1 and XRCC6 in bPOI, which corroborated the significance of DNA repair for POI, and brought up an epigenetic explanation for the disease.
机译:过早的卵巢不足(POI)对妇女的生育和终身健康造成了巨大挑战。 POI是高度异质的,包括神秘的,生化和公开阶段。 MicroRNAs(miRNA)是基因表达的负调节因子,其生理和疾病的作用已经认识到,但是已经认识到癌症和神经紊乱的疾病,但关于MiRNA曲线和生物化学POI(BPOI)的功能相关性毫无少。在该研究中,BPOI妇女的颗粒体细胞(GCS)中miRNA和MRNA的表达分别由两种微阵列测定。 MiR-379-5P,PARP1和XRCC6在BPOI的GCS中差异地表达,如微阵列所揭示的。随后,功能性研究表明MIR-379-5P过表达抑制颗粒细胞增殖并减弱DNA修复效率。此外,PARP1和XRCC6均显示出BPOI患者的GCS中较低的水平,并被鉴定为MIR-379-5P的高管。因此,我们的数据首先揭示了BPOI的潜在致病MiR-379-5P和两种新靶PARP1和XRCC6,其证实了DNA修复对POI的重要性,并为疾病提出了表观遗传解释。

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