title: Novel mechanism of miRNA-365-regulated trophoblast apoptosis in recurrent miscarriage.
abstract: Clinical pregnancies increasingly end in recurrent miscarriage (RM) during the first trimester, with genetic factors shouldering the main responsibility. MicroRNAs (miRNAs) regulate gene expression in a wide array of important biological processes. We examined the potential role of dysregulated miRNAs in RM pathogenesis and trophoblast development as an approach to elucidate the molecular mechanism behind RM. miRNA profiles from clinical specimens of RM and induced abortion (IA) were compared, and several miRNAs were found to be aberrantly expressed in RM samples. Among the miRNAs, miR-365 was significantly differentially expressed in RM decidual tissues. Furthermore, our results demonstrate that miR-365 functions as an upstream regulator of MDM2/p53 expression, cell cycle progression and apoptosis in trophoblasts. Bioinformatic prediction and experimental validation assays identified SGK1 as a direct target of miR-365; consistently, its protein levels were low in decidual tissues. Additionally, functional studies revealed that SGK1 silencing elicits cell cycle arrest and apoptosis in trophoblasts and that SGK1 overexpression attenuates the effects of miR-365 on apoptosis and MDM2/p53 expression. Collectively, our data provide evidence that the up-regulation of miR-365 may contribute to RM by decreasing SGK1 expression, which suggests its potential utility as a prognostic biomarker and therapeutic target for RM.
authors.affiliation: The Fourth School of Clinical Medicine of Nanjing Medical University, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Clinical Laboratory, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Tianfei Alley, Nanjing, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Shen
authors.affiliation: Dunman High School, Singapore City, Singapore.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Clinical Laboratory, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Tianfei Alley, Nanjing, China.
authors.forename: Wen-Yan
authors.initials: WY
authors.lastname: Ding
authors.affiliation: The Fourth School of Clinical Medicine of Nanjing Medical University, Nanjing, China.
authors.forename: Lin-Ping
authors.initials: LP
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Clinical Laboratory, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Tianfei Alley, Nanjing, China.
authors.forename: Ling-Juan
authors.identifier: 0000-0002-9500-3639
authors.initials: LJ
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Clinical Laboratory, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Tianfei Alley, Nanjing, China.
authors.forename: Xiu-Ling
authors.initials: XL
authors.lastname: Li
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Clinical Laboratory, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Tianfei Alley, Nanjing, China.
authors.forename: Tian-Ying
authors.initials: TY
authors.lastname: Zhong
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000026:Abortion, Habitual / Q000235:genetics*; D000028:Abortion, Induced; D000328:Adult; D017209:Apoptosis / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002460:Cell Line; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D046529:Microscopy, Electron, Transmission; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D014327:Trophoblasts / Q000378:metabolism* / Q000648:ultrastructure; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D020413:3' Untranslated Regions; D017874:Immediate-Early Proteins; D035683:MicroRNAs; D017346:Protein Serine-Threonine Kinases; D051736:Proto-Oncogene Proteins c-mdm2; D000099184:Serum-Glucocorticoid Regulated Kinases; C000603399:MIRN-3662 microRNA, human
keywords: Glucocorticoid inducible kinase 1; Recurrent miscarriage; apoptosis; mechanism; miRNA-365