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多囊卵巢综合征伴胰岛素抵抗患者血清中微小RNA的差异表达

Differential expression of microRNA in the serum of patients with polycystic ovary syndrome with insulin resistance.

作者信息

Huo Yan, Ji Shuqing, Yang Hua, Wu Weifan, Yu Lijing, Ren Yajing, Wang Fang

机构信息

Department of Family Planning, the Second Hospital of Tianjin Medical University, Tianjin, China.

出版信息

Ann Transl Med. 2022 Jul;10(14):762. doi: 10.21037/atm-22-2941.

Abstract

BACKGROUND

Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disease in women of childbearing age, and insulin resistance is an important etiological mechanism in PCOS. This study revealed the microRNA (miRNA) expression profile of PCOS with insulin resistance and explored the potential biological functions of differentially expressed miRNA.

METHODS

A total of 76 patients with PCOS and 30 normal healthy women were recruited in the gynecological clinic of the Second Hospital of Tianjin Medical University. We divided the patients with PCOS into a group with insulin resistance (n=46) and a group without insulin resistance (n=30). Peripheral venous serum samples from each group were used for deep sequencing to identify differentially expressed miRNAs. Hierarchical clustering heat maps were used to show differences in miRNA expression. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and target gene network databases were used to explore the potential target genes of differentially expressed miRNAs and to analyze their specific biological functions.

RESULTS

A case-control analysis found that the levels of body mass index (BMI), prolactin (PRL), total testosterone (T), fasting blood glucose (FBG), and fasting insulin (INS) in patients with PCOS were higher than those in healthy controls. High BMI, high blood sugar, and hyperinsulinemia were more significant in the PCOS with insulin resistance group than without insulin resistance group. Among the patients with PCOS, miR-122-5p was found to have more significant differences in the PCOS with insulin resistance group. GO and KEGG pathway analysis showed that the identified miRNAs were involved in the regulation of different biological processes, such as signal transduction, negative regulation of GTPase activity, chloride channel complex. The predicted target genes were related to the citrate cycle (TCA cycle) and the biosynthesis of mucin-type O-glycans.

CONCLUSIONS

Our research demonstrated the use of miRNAs as new biomarkers for the diagnosis, treatment and presented a new strategy to lessen the symptoms of PCOS with insulin resistance.

摘要

背景

多囊卵巢综合征(PCOS)是育龄期女性最常见的生殖内分泌疾病,胰岛素抵抗是PCOS的重要病因机制。本研究揭示了伴有胰岛素抵抗的PCOS患者的微小RNA(miRNA)表达谱,并探讨了差异表达miRNA的潜在生物学功能。

方法

天津医科大学第二医院妇科门诊共招募了76例PCOS患者和30名正常健康女性。我们将PCOS患者分为胰岛素抵抗组(n = 46)和无胰岛素抵抗组(n = 30)。每组的外周静脉血清样本用于深度测序以鉴定差异表达的miRNA。层次聚类热图用于显示miRNA表达的差异。基因本体论(GO)、京都基因与基因组百科全书(KEGG)通路分析以及靶基因网络数据库用于探索差异表达miRNA的潜在靶基因,并分析其特定生物学功能。

结果

病例对照分析发现,PCOS患者的体重指数(BMI)、催乳素(PRL)、总睾酮(T)、空腹血糖(FBG)和空腹胰岛素(INS)水平高于健康对照组。高BMI、高血糖和高胰岛素血症在伴有胰岛素抵抗的PCOS组中比无胰岛素抵抗组更显著。在PCOS患者中,发现miR-122-5p在伴有胰岛素抵抗组中差异更显著。GO和KEGG通路分析表明,鉴定出的miRNA参与不同生物学过程的调控,如信号转导、GTPase活性的负调控、氯离子通道复合体。预测的靶基因与柠檬酸循环(TCA循环)和粘蛋白型O-聚糖的生物合成有关。

结论

我们的研究证明了将miRNA用作诊断、治疗的新生物标志物,并提出了减轻伴有胰岛素抵抗的PCOS症状的新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144a/9372667/ecbe6f783a72/atm-10-14-762-f1.jpg

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