PMID- 22877943 OWN - NLM STAT- MEDLINE DCOM- 20130301 LR - 20201219 IS - 1472-6491 (Electronic) IS - 1472-6483 (Linking) VI - 25 IP - 4 DP - 2012 Oct TI - Evidence that miR-133a causes recurrent spontaneous abortion by reducing HLA-G expression. PG - 415-24 LID - 10.1016/j.rbmo.2012.06.022 [doi] AB - 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. CI - Copyright (c) 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. FAU - Wang, Xiaohong AU - Wang X AD - Department of Obstetrics and Gynecology, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China. xhwang_1968@126.com FAU - Li, Bo AU - Li B FAU - Wang, Jun AU - Wang J FAU - Lei, Jie AU - Lei J FAU - Liu, Chuang AU - Liu C FAU - Ma, Yuan AU - Ma Y FAU - Zhao, Hongxi AU - Zhao H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120720 PL - Netherlands TA - Reprod Biomed Online JT - Reproductive biomedicine online JID - 101122473 RN - 0 (3' Untranslated Regions) RN - 0 (HLA-G Antigens) RN - 0 (MIRN133 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Mutant Proteins) RN - 0 (Recombinant Proteins) SB - IM MH - 3' Untranslated Regions MH - Abortion, Habitual/genetics/*metabolism MH - Adult MH - Cell Line MH - China MH - Chorionic Villi/*metabolism MH - Chorionic Villi Sampling MH - Comparative Genomic Hybridization MH - *Down-Regulation MH - Female MH - Genes, Reporter MH - HLA-G Antigens/genetics/*metabolism MH - Humans MH - Karyotype MH - MicroRNAs/genetics/*metabolism MH - Mutant Proteins/metabolism MH - Pregnancy MH - Pregnancy Trimester, First MH - Recombinant Proteins/metabolism MH - *Up-Regulation EDAT- 2012/08/11 06:00 MHDA- 2013/03/02 06:00 CRDT- 2012/08/11 06:00 PHST- 2012/02/03 00:00 [received] PHST- 2012/06/16 00:00 [revised] PHST- 2012/06/21 00:00 [accepted] PHST- 2012/08/11 06:00 [entrez] PHST- 2012/08/11 06:00 [pubmed] PHST- 2013/03/02 06:00 [medline] AID - S1472-6483(12)00418-X [pii] AID - 10.1016/j.rbmo.2012.06.022 [doi] PST - ppublish SO - Reprod Biomed Online. 2012 Oct;25(4):415-24. doi: 10.1016/j.rbmo.2012.06.022. Epub 2012 Jul 20.