差异表达的环状 RNA 与子痫前期相关的竞争性内源性 RNA 网络。

Differentially expressed circular RNAs and the competing endogenous RNA network associated with preeclampsia.

机构信息

Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China; The Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai, China.

Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.

出版信息

Placenta. 2021 Jan 1;103:232-241. doi: 10.1016/j.placenta.2020.10.010. Epub 2020 Oct 13.

DOI:10.1016/j.placenta.2020.10.010

PMID:33202359

Abstract

INTRODUCTION

Circular RNAs (circRNAs) are non-coding RNAs that are implicated in preeclampsia (PE) pathogenesis; however, their expression and functions in PE remain unclear. In this study, we aimed to investigate the expression of circRNAs in PE and construct a competing endogenous RNA (ceRNA) network, and analyze the associated pathways in PE pathogenesis.

METHODS

We performed circRNA sequencing to identify the differential expression profile of circRNAs in PE as compared to normal pregnancy. The circRNA candidates were validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Subsequently, we used datasets from the GEO database to generate the interaction network between circRNAs, microRNAs (miRNAs), and mRNAs. GO and KEGG enrichment analyses were performed to understand the functional significance of the differentially expressed circRNAs in PE.

RESULTS

We identified 361 differentially expressed circRNAs (252 upregulated and 109 downregulated) in preeclamptic placentas. Within the selected 31 circRNAs, 6 of them were verified by qRT-PCR. GO and KEGG analyses revealed the potential pathways affected by these circRNAs, e.g., T cell receptor signaling and MAP kinase pathways. A total of 134 miRNAs and 199 mRNAs were revealed to be differentially expressed in PE by analyzing datasets from the GEO database. The circRNA-miRNA-mRNA network comprised 206 circRNAs, 50 miRNAs, and 38 mRNAs. KEGG analysis of the 38 mRNAs included pathways involved in AMPK and PI3K-Akt signaling.

DISCUSSION

Our results reported the differential expression profile of circRNAs and the circRNA-miRNA-mRNA network in PE, which provides potential therapeutic targets for this disease.

摘要

简介

环状 RNA（circRNAs）是非编码 RNA，被认为与子痫前期（PE）的发病机制有关；然而，其在 PE 中的表达和功能尚不清楚。在这项研究中，我们旨在研究 circRNAs 在 PE 中的表达，构建竞争性内源 RNA（ceRNA）网络，并分析 PE 发病机制中的相关途径。

方法

我们进行了 circRNA 测序，以鉴定与正常妊娠相比 PE 中 circRNAs 的差异表达谱。使用定量逆转录聚合酶链反应（qRT-PCR）验证 circRNA 候选物。随后，我们使用 GEO 数据库中的数据集生成 circRNA、microRNA（miRNA）和 mRNA 之间的相互作用网络。进行 GO 和 KEGG 富集分析以了解差异表达的 circRNAs 在 PE 中的功能意义。

结果

我们在子痫前期胎盘中共鉴定出 361 个差异表达的 circRNAs（252 个上调和 109 个下调）。在选定的 31 个 circRNAs 中，有 6 个通过 qRT-PCR 验证。GO 和 KEGG 分析显示，这些 circRNAs 可能影响 T 细胞受体信号和 MAP 激酶途径等途径。通过分析 GEO 数据库中的数据集，发现 PE 中共有 134 个 miRNA 和 199 个 mRNA 表达差异。circRNA-miRNA-mRNA 网络包括 206 个 circRNAs、50 个 miRNA 和 38 个 mRNA。对 38 个 mRNA 的 KEGG 分析包括 AMPK 和 PI3K-Akt 信号通路。