title: Identification of altered microRNAs and mRNAs in the cumulus cells of PCOS patients: miRNA-509-3p promotes oestradiol secretion by targeting MAP3K8.
abstract: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women and is characterised by polycystic ovaries, hyperandrogenism and chronic anovulation. Although the clinical and biochemical signs of PCOS are typically heterogeneous, abnormal folliculogenesis is considered a common characteristic of PCOS. Our aim is to identify the altered miRNA and mRNA expression profiles in the cumulus cells of PCOS patients to investigate their molecular function in the aetiology and pathophysiology of PCOS. In this study, the miRNA expression profiles of the cumulus cell samples isolated from five PCOS and five control patients were determined by an miRNA microarray. At the same time, the altered mRNA profiles of the same cumulus cell samples were also identified by a cDNA microarray. From the microarray data, 17 miRNAs and 1263 mRNAs showed significantly different expression in the PCOS cumulus cells. The differentially expressed miRNA-509-3p and its potential target gene (MAP3K8) were identified from the miRNA and mRNA microarrays respectively. The expression of miRNA-509-3p was up-regulated and MAP3K8 was down-regulated in the PCOS cumulus cells. The direct interaction between miRNA-509-3p and MAP3K8 was confirmed by a luciferase activity assay in KGN cells. In addition, miRNA-509-3p mimics or inhibitor transfection tests in KGN cells further confirmed that miRNA-509-3p improved oestradiol (E2) secretion by inhibiting the expression of MAP3K8 These results help to characterise the pathogenesis of anovulation in PCOS, especially the regulation of E2 production.
authors.affiliation: Reproductive Medicine CentreAffiliated Hospital of Qingdao Medical University, Yuhuangding Hospital of Yantai, Yantai, Shandong, People's Republic of China huangxin92129@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Shandong University School of MedicineJinan, Shandong, People's Republic of China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Reproductive Medicine CentreAffiliated Hospital of Qingdao Medical University, Yuhuangding Hospital of Yantai, Yantai, Shandong, People's Republic of China.
authors.forename: Cuifang
authors.initials: C
authors.lastname: Hao
authors.affiliation: Department of LaboratoryAffiliated Hospital of Qingdao Medical University, Yuhuangding Hospital of Yantai, Yantai, Shandong, People's Republic of China.
authors.forename: Qianqing
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of LaboratoryAffiliated Hospital of Qingdao Medical University, Yuhuangding Hospital of Yantai, Yantai, Shandong, People's Republic of China.
authors.forename: Riming
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of LaboratoryAffiliated Hospital of Qingdao Medical University, Yuhuangding Hospital of Yantai, Yantai, Shandong, People's Republic of China.
authors.forename: Shaoxia
authors.initials: S
authors.lastname: Lin
authors.affiliation: Reproductive Medicine CentreAffiliated Hospital of Qingdao Medical University, Yuhuangding Hospital of Yantai, Yantai, Shandong, People's Republic of China.
authors.forename: Luping
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Reproductive Medicine CentreAffiliated Hospital of Qingdao Medical University, Yuhuangding Hospital of Yantai, Yantai, Shandong, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002450:Cell Communication; D002478:Cells, Cultured; D054885:Cumulus Cells / Q000378:metabolism* / Q000473:pathology; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: C571982:MIRN509 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D004958:Estradiol; D020930:MAP Kinase Kinase Kinases; C069937:MAP3K8 protein, human