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探讨 ceRNA 网络中包含 AGAP2-AS1 的新的子痫前期生物标志物。

Exploring the ceRNA network involving AGAP2-AS1 as a novel biomarker for preeclampsia.

机构信息

Department of Obstetrics, Affiliated Hospital of GuiZhou Medical University, Guiyang, Guizhou, China.

Department of Hospital infection and control, Affiliated Hospital of GuiZhou Medical University, Guiyang, Guizhou, China.

出版信息

Sci Rep. 2024 Nov 9;14(1):27330. doi: 10.1038/s41598-024-79224-2.

Abstract

Preeclampsia (PE) is an important research subject in obstetrics. Nevertheless, the underlying mechanisms of PE remain elusive. PE-related expression datasets (GSE96983, GSE96984 and GSE24129) were downloaded from the Gene Expression Omnibus (GEO) database. Firstly, the differentially expressed messenger RNAs (DE-mRNAs), DE-microRNA (DE-miRNAs) and DE-long non-coding RNA (DE-lncRNAs) between PE and control cohorts were identified, and the ceRNA network was constructed. Then candidate hub genes were obtained through five algorithms by the protein-protein intersection (PPI) network of the mRNAs. Further, five hub genes were identified by receiver operating characteristic (ROC) curve and gene expression profiles: DAXX, EFNB1, NCOR2, RBBP4 and SOCS1. The function of 5 hub genes was analyzed and the interaction between drugs and hub genes was predicted. A total of 5 small molecule drugs were predicted, namely benzbromarone, 9,10-phenanthrenequinone, chembl312032, insulin and aldesleukin. AGAP2-AS1 was mainly located in exosome and cytoplasm. Agap2-as1-related regulatory subnetworks were extracted from ceRNA networks which included 41 mRNAs, 2 miRNAs and 1 lncRNA, including the regulated relationship pairs AGAP2-AS1-hsa-miR-497-5p-SRPRB, and AGAP2-AS1-hsa-miR-195-5p-RPL36. In summary, we constructed a competitive endogenous RNA (ceRNA) network to identify five potential biomarkers (DAXX, EFNB1, NCOR2, SOCS1 and RBBP4) of PE. The in-depth analysis of the AGAP2-AS1 regulatory network will help to uncover more important molecules closely related to PE and provide a scientific Reference.

摘要

子痫前期 (PE) 是妇产科的重要研究课题。然而,PE 的潜在机制仍难以捉摸。从基因表达综合数据库 (GEO) 下载了与 PE 相关的表达数据集 (GSE96983、GSE96984 和 GSE24129)。首先,鉴定了 PE 与对照组之间差异表达的信使 RNA (DE-mRNA)、差异表达 microRNA (DE-miRNA) 和差异表达长非编码 RNA (DE-lncRNA),并构建了 ceRNA 网络。然后,通过五种算法,根据 mRNAs 的蛋白质-蛋白质相互作用 (PPI) 网络,获得候选枢纽基因。进一步通过 ROC 曲线和基因表达谱确定了 5 个枢纽基因:DAXX、EFNB1、NCOR2、RBBP4 和 SOCS1。分析了 5 个枢纽基因的功能,并预测了药物与枢纽基因的相互作用。预测了 5 种小分子药物,分别为苯溴马隆、9,10-菲醌、chembl312032、胰岛素和白细胞介素。AGAP2-AS1 主要位于外泌体和细胞质中。从 ceRNA 网络中提取了与 AGAP2-AS1 相关的调节子网络,该网络包含 41 个 mRNA、2 个 miRNA 和 1 个 lncRNA,包括调节关系对 AGAP2-AS1-hsa-miR-497-5p-SRPRB 和 AGAP2-AS1-hsa-miR-195-5p-RPL36。总之,我们构建了一个竞争性内源性 RNA (ceRNA) 网络,以鉴定 5 个潜在的 PE 生物标志物 (DAXX、EFNB1、NCOR2、SOCS1 和 RBBP4)。对 AGAP2-AS1 调控网络的深入分析将有助于发现更多与 PE 密切相关的重要分子,为其提供科学参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d07/11550820/84de98fa66f1/41598_2024_79224_Fig1_HTML.jpg

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