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血清miR-379在肥胖-多囊卵巢综合征中的临床价值及机制探讨

Clinical Value and Mechanism Exploration of Serum miR-379 in Obesity-Polycystic Ovary Syndrome.

作者信息

Huang Lu, Fu Yujing, Cao Jinghong, Zhai Jianjun

机构信息

Department of Obstetrics and Gynecology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People's Republic of China.

出版信息

Int J Womens Health. 2024 Jun 21;16:1149-1157. doi: 10.2147/IJWH.S427997. eCollection 2024.

Abstract

OBJECTIVE

As a common endocrine and metabolic disorder, polycystic ovary syndrome (PCOS) is mostly associated with an obese phenotype. The present research focuses on the clinical significance of miR-379 in obesity-PCOS and attempts to elucidate its potential mechanisms.

METHODS

Healthy individuals (n = 46), obesity-PCOS (n = 92), and non-obesity PCOS (n = 31) subjects were enrolled. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to examine the level of serum miR-379. The receiver operating characteristic (ROC) curve and logistic regressions were applied to reveal the diagnostic significance. Dual luciferase reporters were performed to validate the targeting relationships. And cell count kit (CCK-8) assay was used to detect cell proliferation.

RESULTS

Serum miR-379 was highly expressed in PCOS patients ( < 0.05), in especially obesity-PCOS patients. Higher miR-379 was associated with greater body mass index (BMI), higher bioavailable testosterone (bT), and greater insulin resistance (IR). Additionally, miR-379 was an independent risk factor for the development of obesity-PCOS. The sensitivity of miR-379 in identifying patients with obesity-PCOS from healthy or non-obesity-PCSO patients was 81.52% and 72.83%, and the specificity was 86.96% and 80.65%. Semaphorin 3 A (SEMA3A) was identified as a target of miR-379 and was reduced in the patients with obesity PCOS (P < 0.05). Inhibition of miR-375 reduced KGN proliferation, but this reduction was partially restored by silencing of SEMA3A ( < 0.05).

CONCLUSION

Elevated miR-379 assists the diagnosis of obesity-PCOS and regulates the proliferation of KGN by targeting SEMA3A engaged in disease development.

摘要

目的

多囊卵巢综合征(PCOS)作为一种常见的内分泌和代谢紊乱疾病,大多与肥胖表型相关。本研究聚焦于miR-379在肥胖型PCOS中的临床意义,并试图阐明其潜在机制。

方法

招募健康个体(n = 46)、肥胖型PCOS患者(n = 92)和非肥胖型PCOS患者(n = 31)。采用定量实时聚合酶链反应(qRT-PCR)检测血清miR-379水平。应用受试者工作特征(ROC)曲线和逻辑回归分析来揭示其诊断意义。进行双荧光素酶报告基因实验以验证靶向关系。并使用细胞计数试剂盒(CCK-8)检测细胞增殖。

结果

血清miR-379在PCOS患者中高表达(<0.05),尤其是肥胖型PCOS患者。较高的miR-379与更高的体重指数(BMI)、更高的生物可利用睾酮(bT)和更大的胰岛素抵抗(IR)相关。此外,miR-379是肥胖型PCOS发生的独立危险因素。miR-379从健康或非肥胖型PCOS患者中识别肥胖型PCOS患者的敏感性分别为81.52%和72.83%,特异性分别为86.96%和80.65%。信号素3A(SEMA3A)被确定为miR-379的靶点,且在肥胖型PCOS患者中降低(P < 0.05)。抑制miR-375可降低KGN细胞增殖,但通过沉默SEMA3A可部分恢复这种降低(<0.05)。

结论

miR-379升高有助于肥胖型PCOS的诊断,并通过靶向参与疾病发展的SEMA3A调节KGN细胞增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfde/11198001/6d5a91f1f5a0/IJWH-16-1149-g0003.jpg

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