Identification of several circulating microRNAs from a genome-wide circulating microRNA expression profile as potential

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ORIGINAL ARTICLE

Identification of several circulating microRNAs from a genomewide circulating microRNA expression profile as potential biomarkers for impaired glucose metabolism in polycystic ovarian syndrome Linlin Jiang1 • Jia Huang1 • Yaxiao Chen1 • Yabo Yang1 • Ruiqi Li1 Yu Li1 • Xiaoli Chen1 • Dongzi Yang1



Received: 21 April 2015 / Accepted: 21 January 2016 Ó Springer Science+Business Media New York 2016

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 assessmentinsulin 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. Keywords Circulating miRNAs  Polycystic ovarian syndrome  Impaired glucose metabolism  Biomarker 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

Linlin Jiang and Jia Huang have contributed equally.

Electronic supplementary material The online version of this article (doi:10.1007/s12020-016-0878-9) contains supplementary material, which is available to authorized users. & Dongzi Yang [email protected] 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

Introduction Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases, with a prevalence of approximately 7 % in prem