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胎儿膜的长链非编码 RNA 和转录组分析揭示了与羊水过少相关的潜在靶点。

LncRNA and transcriptomic analysis of fetal membrane reveal potential targets involved in oligohydramnios.

机构信息

Department of Obstetrics and Gynecology, Guangdong Women and Children Hospital, Guangzhou, 511400, Guangdong, China.

Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No.107, Yanjiangxi Road, Guangzhou, 510120, Guangdong, China.

出版信息

BMC Med Genomics. 2020 Sep 18;13(1):137. doi: 10.1186/s12920-020-00792-z.

Abstract

BACKGROUND

The multiple causes of oligohydramnios make it challenging to study. Long noncoding RNAs (lncRNAs) are sets of RNAs that have been proven to function in multiple biological processes. The purpose of this study is to study expression level and possible role of lncRNAs in oligohydramnios.

METHODS

In this study, total RNA was isolated from fetal membranes resected from oligohydramnios pregnant women (OP) and normal amount of amniotic fluid pregnant women (Normal). LncRNA microarray was used to analyze the differentially expressed lncRNAs and mRNAs. Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to analyze the main enrichment pathways of differentially expressed mRNAs. Real-time quantitative PCR (qPCR) was used to validate the lncRNA expression level.

RESULTS

LncRNA microarray analysis revealed that a total of 801 lncRNAs and 367 mRNAs were differentially expressed in OP; in these results, 638 lncRNAs and 189 mRNAs were upregulated, and 163 lncRNAs and 178 mRNAs were downregulated. Of the lncRNAs, 566 were intergenic lncRNAs, 351 were intronic antisense lncRNAs, and 300 were natural antisense lncRNAs. The differentially expressed lncRNAs were primarily located in chromosomes 2, 1, and 11. KEGG enrichment pathways revealed that the differentially expressed mRNAs were enriched in focal adhesion as well as in the signaling pathways of Ras, tumor necrosis factor (TNF), estrogen, and chemokine. The qPCR results confirmed that LINC00515 and RP11-388P9.2 were upregulated in OP. Furthermore, the constructed lncRNA-miRNA-mRNA regulatory network revealed tenascin R (TNR), cystic fibrosis transmembrane conductance regulator (CFTR), ATP-binding cassette sub-family A member 12 (ABCA12), and collagen 9A2 (COL9A2) as the candidate targets of LINC00515 and RP11-388P9.2.

CONCLUSIONS

In summary, we revealed the profiles of lncRNA and mRNA in OP. These results might offer potential targets for biological prevention for pregnant women with oligohydramnios detected before delivery and provided a reliable basis for clinical biological treatment in OP.

摘要

背景

羊水过少的病因众多,因此难以研究。长链非编码 RNA(lncRNA)是一组已被证明在多种生物学过程中发挥作用的 RNA。本研究旨在研究 lncRNA 在羊水过少中的表达水平和可能的作用。

方法

本研究从羊水过少孕妇(OP)和羊水正常孕妇(Normal)的胎膜中分离总 RNA,采用 lncRNA 微阵列分析差异表达的 lncRNA 和 mRNA。京都基因与基因组百科全书(KEGG)用于分析差异表达 mRNA 的主要富集途径。实时定量 PCR(qPCR)用于验证 lncRNA 的表达水平。

结果

lncRNA 微阵列分析显示,OP 中共有 801 个 lncRNA 和 367 个 mRNA 差异表达,其中 638 个 lncRNA 和 189 个 mRNA 上调,163 个 lncRNA 和 178 个 mRNA 下调。在这些 lncRNA 中,566 个是基因间 lncRNA,351 个是内含子反义 lncRNA,300 个是天然反义 lncRNA。差异表达的 lncRNA 主要位于染色体 2、1 和 11 上。KEGG 富集途径显示,差异表达的 mRNA 富集在粘着斑以及 Ras、肿瘤坏死因子(TNF)、雌激素和趋化因子信号通路中。qPCR 结果证实,LINC00515 和 RP11-388P9.2 在 OP 中上调。此外,构建的 lncRNA-miRNA-mRNA 调控网络显示 tenascin R(TNR)、囊性纤维化跨膜电导调节剂(CFTR)、ATP 结合盒亚家族 A 成员 12(ABCA12)和胶原 9A2(COL9A2)是 LINC00515 和 RP11-388P9.2 的候选靶标。

结论

总之,我们揭示了 OP 中 lncRNA 和 mRNA 的特征。这些结果可能为产前检测羊水过少的孕妇提供生物预防的潜在靶点,并为 OP 的临床生物治疗提供可靠依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc94/7501699/7d61bf69b5ed/12920_2020_792_Fig1_HTML.jpg

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