Cargando…
Novel mechanism of miRNA‐365‐regulated trophoblast apoptosis in recurrent miscarriage
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 miRN...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618703/ https://www.ncbi.nlm.nih.gov/pubmed/28393453 http://dx.doi.org/10.1111/jcmm.13163 |
_version_ | 1783267249091510272 |
---|---|
author | Zhao, Wei Shen, Wei‐wei Cao, Xiao‐mei Ding, Wen‐yan Yan, Lin‐ping Gao, Ling‐juan Li, Xiu‐Ling Zhong, Tian‐ying |
author_facet | Zhao, Wei Shen, Wei‐wei Cao, Xiao‐mei Ding, Wen‐yan Yan, Lin‐ping Gao, Ling‐juan Li, Xiu‐Ling Zhong, Tian‐ying |
author_sort | Zhao, Wei |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5618703 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-56187032017-10-04 Novel mechanism of miRNA‐365‐regulated trophoblast apoptosis in recurrent miscarriage Zhao, Wei Shen, Wei‐wei Cao, Xiao‐mei Ding, Wen‐yan Yan, Lin‐ping Gao, Ling‐juan Li, Xiu‐Ling Zhong, Tian‐ying J Cell Mol Med Original Articles 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. John Wiley and Sons Inc. 2017-04-10 2017-10 /pmc/articles/PMC5618703/ /pubmed/28393453 http://dx.doi.org/10.1111/jcmm.13163 Text en © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Zhao, Wei Shen, Wei‐wei Cao, Xiao‐mei Ding, Wen‐yan Yan, Lin‐ping Gao, Ling‐juan Li, Xiu‐Ling Zhong, Tian‐ying Novel mechanism of miRNA‐365‐regulated trophoblast apoptosis in recurrent miscarriage |
title | Novel mechanism of miRNA‐365‐regulated trophoblast apoptosis in recurrent miscarriage |
title_full | Novel mechanism of miRNA‐365‐regulated trophoblast apoptosis in recurrent miscarriage |
title_fullStr | Novel mechanism of miRNA‐365‐regulated trophoblast apoptosis in recurrent miscarriage |
title_full_unstemmed | Novel mechanism of miRNA‐365‐regulated trophoblast apoptosis in recurrent miscarriage |
title_short | Novel mechanism of miRNA‐365‐regulated trophoblast apoptosis in recurrent miscarriage |
title_sort | novel mechanism of mirna‐365‐regulated trophoblast apoptosis in recurrent miscarriage |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618703/ https://www.ncbi.nlm.nih.gov/pubmed/28393453 http://dx.doi.org/10.1111/jcmm.13163 |
work_keys_str_mv | AT zhaowei novelmechanismofmirna365regulatedtrophoblastapoptosisinrecurrentmiscarriage AT shenweiwei novelmechanismofmirna365regulatedtrophoblastapoptosisinrecurrentmiscarriage AT caoxiaomei novelmechanismofmirna365regulatedtrophoblastapoptosisinrecurrentmiscarriage AT dingwenyan novelmechanismofmirna365regulatedtrophoblastapoptosisinrecurrentmiscarriage AT yanlinping novelmechanismofmirna365regulatedtrophoblastapoptosisinrecurrentmiscarriage AT gaolingjuan novelmechanismofmirna365regulatedtrophoblastapoptosisinrecurrentmiscarriage AT lixiuling novelmechanismofmirna365regulatedtrophoblastapoptosisinrecurrentmiscarriage AT zhongtianying novelmechanismofmirna365regulatedtrophoblastapoptosisinrecurrentmiscarriage |