title: The role, mechanism and potentially novel biomarker of microRNA-17-92 cluster in macrosomia.
abstract: Macrosomia is one of the most common perinatal complications of pregnancy and has life-long health implications for the infant. microRNAs (miRNAs) have been identified to regulate placental development, yet the role of miRNAs in macrosomia remains poorly understood. Here we investigated the role of miR-17-92 cluster in macrosomia. The expression levels of five miRNAs in miR-17-92 cluster were significantly elevated in placentas of macrosomia, which may due to the up-regulation of miRNA-processing enzyme Drosha and Dicer. Cell cycle pathway was identified to be the most relevant pathways regulated by miR-17-92 cluster miRNAs. Importantly, miR-17-92 cluster increased proliferation, attenuated cell apoptosis and accelerated cells entering S phase by targeting SMAD4 and RB1 in HTR8/SVneo cells. Furthermore, we found that expression of miR-17-92 cluster in serum had a high diagnostic sensitivity and specificity for macrosomia (AUC: 80.53%; sensitivity: 82.61%; specificity: 69.57%). Our results suggested that miR-17-92 cluster contribute to macrosomia development by targeting regulators of cell cycle pathway. Our findings not only provide a novel insight into the molecular mechanisms of macrosomia, but also the clinical value of miR-17-92 cluster as a predictive biomarker for macrosomia.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.|Department of Public Health, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.|Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Nantong University, Nantong, 226001, China.|Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Obstetrics, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210004, China.
authors.lastname: Qiuqin Tang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.|State Key Laboratory of Reproductive Medicine, Wuxi Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi 214002, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.lastname: Hao Gu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Wuxi Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi 214002, China.
authors.lastname: Lou Liu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Wuxi Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi 214002, China.
authors.lastname: Jie Wu
authors.affiliation: Perinatology Unit, Changzhou Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Changzhou 213003, China.
authors.lastname: Hua Jiang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Obstetrics, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210004, China.
authors.lastname: Hongjuan Ding
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Reproductive Medicine, Wuxi Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi 214002, China.
authors.forename: Daozhen
authors.initials: D
authors.lastname: Chen
authors.affiliation: Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
mesh_terms: D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D001724:Birth Weight; D016022:Case-Control Studies; D002460:Cell Line; D049109:Cell Proliferation; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D005260:Female; D005320:Fetal Macrosomia / Q000175:diagnosis / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007231:Infant, Newborn; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D034622:RNA Interference; D012372:ROC Curve; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C524941:MIRN17 microRNA, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D016160:Retinoblastoma Protein; C497796:SMAD4 protein, human; D051901:Smad4 Protein; C408087:DICER1 protein, human; C517918:DROSHA protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases