title: Evidence that miR-133a causes recurrent spontaneous abortion by reducing HLA-G expression.
abstract: Human leukocyte antigen (HLA)-G is thought to confer fetal-maternal tolerance and play a crucial role in ensuring a successful pregnancy. There is increasing evidence that HLA-G is regulated at the post-transcriptional level. This study investigated the role of miR-133a in regulating HLA-G expression and the pathogenesis of recurrent spontaneous abortion (RSA). Twelve patients (25-30 years) with RSA at 7 gestational weeks were screened by array-based comparative genome hybridization: 16.7% were found to have an abnormal karyotype and all induced abortion (IA) patients had normal karyotype. The villi of RSA and IA patients with normal karyotype were further screened by miRNA microarrays. Multi-software prediction and real-time PCR confirmed that miR-133a was most likely to bind to HLA-G 3' untranscribed region (UTR). Relevance analysis showed that, compared with IA villi, miR-133a was greatly overexpressed in RSA villi with normal karyotype (P<0.01), but not in abnormal RSA villi. A luciferase reporter assay suggested that miR-133a interacted with HLA-G 3' UTR. Overexpression of miR-133a in JEG-3 cells decreased HLA-G expression at the protein level, with no effect on mRNA. These findings provide strong evidence that miR-133a regulates HLA-G expression by reducing translation and is involved in the pathogenesis of RSA.
authors.affiliation: Department of Obstetrics and Gynecology, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China. xhwang_1968@126.com
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Lei
authors.forename: Chuang
authors.initials: C
authors.lastname: Liu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ma
authors.forename: Hongxi
authors.initials: H
authors.lastname: Zhao
mesh_terms: D020413:3' Untranslated Regions; D000026:Abortion, Habitual / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D002460:Cell Line; D002681:China; D002824:Chorionic Villi / Q000378:metabolism*; D015193:Chorionic Villi Sampling; D055028:Comparative Genomic Hybridization; D015536:Down-Regulation; D005260:Female; D017930:Genes, Reporter; D059951:HLA-G Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D059785:Karyotype; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011994:Recombinant Proteins / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D059951:HLA-G Antigens; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D050505:Mutant Proteins; D011994:Recombinant Proteins