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人类卵母细胞和囊胚中微小RNA表达及DNA修复基因转录本的研究。

Investigation of microRNA expression and DNA repair gene transcripts in human oocytes and blastocysts.

作者信息

Tulay P, Naja R P, Cascales-Roman O, Doshi A, Serhal P, SenGupta S B

机构信息

Faculty of Medicine, Medical Genetics Department, Near East University, Yakin Dogu Bulvari, Nicosia, Cyprus.

UCL Centre for PGD, Institute for Women's Health, University College London, London, UK.

出版信息

J Assist Reprod Genet. 2015 Dec;32(12):1757-64. doi: 10.1007/s10815-015-0585-0. Epub 2015 Oct 5.

Abstract

PURPOSE

The aim of the study is to investigate the regulation of DNA repair genes by microRNAs (miRNAs). miRNAs are short non-coding RNAs that regulate transcriptional and post-transcriptional gene silencing. Several miRNAs that are expressed during preimplantation embryo development have been shown or are predicted to target genes that regulate cell cycle checkpoints and DNA repair in response to DNA damage.

METHODS

This study compares the expression level of 20 miRNAs and 9 target transcripts involved in DNA repair. The statistical significance of differential miRNA expression between oocytes and blastocysts was determined by t test analysis using the GraphPad Prism v6 software. The possible regulatory roles of miRNAs on their target messenger RNAs (mRNAs) were analysed using a Pearson correlation test.

RESULTS

This study shows for the first time that several miRNAs are expressed in human oocytes and blastocysts that target key genes involved in DNA repair and cell cycle checkpoints. Blastocysts exhibited statistically significant lower expression levels for the majority of miRNAs compared to oocytes (p < 0.05). Correlation analyses showed that there was both inverse and direct association between miRNAs and their target mRNAs.

CONCLUSIONS

miRNAs target many mRNAs including ones involved in DNA repair mechanisms. This study suggests that miRNAs and their target mRNAs involved in DNA repair are expressed in preimplantation embryos. Similar to the miRNAs expressed in adult tissues, these miRNAs seem to have regulatory roles on their target DNA repair mRNAs during preimplantation embryo development.

摘要

目的

本研究旨在调查微小RNA(miRNA)对DNA修复基因的调控作用。miRNA是一类短的非编码RNA,可调控转录和转录后基因沉默。已有研究表明,在植入前胚胎发育过程中表达的几种miRNA能够靶向调控细胞周期检查点和DNA损伤后DNA修复的基因,还有一些miRNA的作用也已得到预测。

方法

本研究比较了20种参与DNA修复的miRNA和9种靶转录本的表达水平。使用GraphPad Prism v6软件通过t检验分析确定卵母细胞和囊胚之间miRNA差异表达的统计学意义。使用Pearson相关检验分析miRNA对其靶信使核糖核酸(mRNA)的潜在调控作用。

结果

本研究首次表明,在人类卵母细胞和囊胚中表达的几种miRNA能够靶向参与DNA修复和细胞周期检查点的关键基因。与卵母细胞相比,囊胚中大多数miRNA的表达水平在统计学上显著降低(p < 0.05)。相关性分析表明,miRNA与其靶mRNA之间存在负相关和正相关。

结论

miRNA靶向许多mRNA,包括参与DNA修复机制的mRNA。本研究表明,参与DNA修复的miRNA及其靶mRNA在植入前胚胎中表达。与在成体组织中表达miRNA类似,这些miRNA在植入前胚胎发育过程中似乎对其靶DNA修复mRNA具有调控作用。

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