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Identification of several circulating microRNAs from a genome-wide circulating microRNA expression profile as potential biomarkers for impaired glucose metabolism in polycystic ovarian syndrome

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Abstract

This study aimed to detect serum microRNAs (miRNAs) differentially expressed between polycystic ovary syndrome (PCOS) patients with impaired glucose metabolism (IGM), PCOS patients with normal glucose tolerance (NGT), and healthy controls. A TaqMan miRNA array explored serum miRNA profiles as a pilot study, then selected miRNAs were analyzed in a validation cohort consisting of 65 PCOS women with IGM, 65 PCOS women with NGT, and 45 healthy women The relative expression of miR-122, miR-193b, and miR-194 was up-regulated in PCOS patients compared with controls, whereas that of miR-199b-5p was down-regulated. Furthermore, miR-122, miR-193b, and miR-194 were increased in the PCOS-IGM group compared with the PCOS-NGT group. Multiple linear regression analyses revealed that miR-193b and body mass index contributed independently to explain 43.7 % (P < 0.0001) of homeostasis model assessment-insulin resistance after adjustment for age. Investigation of diagnostic values confirmed the optimal combination of BMI and miR-193b to explore the possibility of IGM in PCOS women with area under the curve of 0.752 (95 % CI 0.667–0.837, P < 0.001). Bioinformatics analysis indicated that the predicted target functions of these miRNAs mainly involved glycometabolism and ovarian follicle development pathways, including the insulin signaling pathway, the neurotrophin signaling pathway, the PI3K-AKT signaling pathway, and regulation of actin cytoskeleton. This study expands our knowledge of the serum miRNA expression profiles of PCOS patients with IGM and the predicted target signal pathways involved in disease pathophysiology.

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Abbreviations

PCOS:

Polycystic ovarian syndrome

IGM:

Impaired glucose metabolism

IGT:

Impaired glucose tolerance

T2DM:

Type 2 diabetes mellitus

NGT:

Normal glucose tolerance

HOMA-IR:

Homeostasis model assessment-insulin resistance

FAI:

Free androgen index

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Acknowledgments

This work was supported by a grant from the Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology (Grant No. [2013]163). Grant support was also provided by the National Natural Science Foundation of China (Grant No. 81370680 and 81402168); the Specialized Research Fund for the Doctoral Program of the Chinese Ministry of Education (Grant No. 20130171130009); the Natural Science Foundation of Key Research Project of Guangdong Province (Grant No: 2013020012660); and the Fund of Natural Science Foundation of Guangdong Province, China (Grant No. 2014A030310069).

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    1. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang West Road, Guangzhou, 510120, People’s Republic of China

      Linlin Jiang, Jia Huang, Yaxiao Chen, Yabo Yang, Ruiqi Li, Yu Li, Xiaoli Chen & Dongzi Yang

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    12020_2016_878_MOESM1_ESM.tif

    miRNA expression in the PCOS-IGM subgroups. Box plots show miRNA expression levels in sera from PCOS-IFG/IGT patients (n = 48) and PCOS-T2DM patients (n = 17). The concentrations of miR-122 (a), miR-193b (b), miR-194 (c), and miR-199b-5p (d) did not differ significantly between the two groups (TIFF 877 kb)

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    Jiang, L., Huang, J., Chen, Y. et al. Identification of several circulating microRNAs from a genome-wide circulating microRNA expression profile as potential biomarkers for impaired glucose metabolism in polycystic ovarian syndrome. Endocrine 53, 280–290 (2016). https://doi.org/10.1007/s12020-016-0878-9

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