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雷公藤多苷治疗的Aβ诱导AD小鼠海马中的长链非编码RNA和环状RNA表达谱

lncRNA and circRNA expression profiles in the hippocampus of Aβ‑induced AD mice treated with Tripterygium glycoside.

作者信息

Tang Liang, Wang Yan, Xiang Ju, Yang Dawei, Zhang Yan, Xiang Qin, Li Jianming

机构信息

Department of Basic Biology, Changsha Medical College, Changsha, Hunan 410219, P.R. China.

Department of Basic Biology, Wuzhou Medical College, Wuzhou, Guangxi Zhuang 543000, P.R. China.

出版信息

Exp Ther Med. 2023 Jul 19;26(3):426. doi: 10.3892/etm.2023.12125. eCollection 2023 Sep.

Abstract

Tripterygium glycosides (TG) have been reported to ameliorate Alzheimer's disease (AD), although the mechanism involved remains to be determined. In the present study, the lncRNA and circRNA expression profiles of an AD mouse model treated with TG were assessed using microarrays. lncRNAs, mRNAs, and circRNAs in the hippocampi of 3 AD+normal saline (NS) mice and 3 AD+TG mice were detected using microarrays. The most differentially expressed lncRNAs, mRNAs, and circRNAs were screened between the AD+NS and AD+TG groups. The differentially expressed lncRNAs and circRNAs were analyzed using GO enrichment and KEGG analyses. Co-expression analysis of lncRNAs, circRNAs, and mRNAs was performed by calculating the correlation coefficients. Protein-protein interaction (PPI) network analysis was performed on mRNAs using STRING. The lncRNA-target-transcription factor (TF) network was analyzed using the Network software. In total, 661 lncRNAs, 64 circRNAs, and 503 mRNAs were found to be differentially expressed in AD mice treated with TG. Pou4f1, Egr2, Mag, and Nr4a1 were the hub genes in the PPI network. The KEGG results showed that the mRNAs that were co-expressed with lncRNAs were enriched in the TNF, PI3K-Akt, and Wnt signaling pathways. LncRNA-target-TF network analysis indicated that TFs, including Cebpa, Zic2, and Rxra, were the most likely to regulate the detected lncRNAs. The circRNA-miRNA interaction network indicated that 275 miRNAs may bind to the 64 circRNAs. In conclusion, these findings provide a novel perspective on AD pathogenesis, and the detected lncRNAs, mRNAs, and circRNAs may serve as novel therapeutic targets for the management of AD.

摘要

雷公藤多苷(TG)据报道可改善阿尔茨海默病(AD),尽管其涉及的机制仍有待确定。在本研究中,使用微阵列评估了用TG治疗的AD小鼠模型的长链非编码RNA(lncRNA)和环状RNA(circRNA)表达谱。使用微阵列检测了3只AD + 生理盐水(NS)小鼠和3只AD + TG小鼠海马中的lncRNA、mRNA和circRNA。在AD + NS组和AD + TG组之间筛选出差异表达最显著的lncRNA、mRNA和circRNA。使用基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)分析对差异表达的lncRNA和circRNA进行分析。通过计算相关系数对lncRNA、circRNA和mRNA进行共表达分析。使用STRING对mRNA进行蛋白质 - 蛋白质相互作用(PPI)网络分析。使用Network软件分析lncRNA - 靶标 - 转录因子(TF)网络。总共发现661种lncRNA、64种circRNA和503种mRNA在用TG治疗的AD小鼠中差异表达。Pou4f1、Egr2、Mag和Nr4a1是PPI网络中的枢纽基因。KEGG结果表明,与lncRNA共表达的mRNA在肿瘤坏死因子(TNF)、磷脂酰肌醇 - 3激酶 - 蛋白激酶B(PI3K - Akt)和Wnt信号通路中富集。lncRNA - 靶标 - TF网络分析表明,包括Cebpa、Zic2和Rxra在内的转录因子最有可能调控检测到的lncRNA。circRNA - 微小RNA(miRNA)相互作用网络表明,275种miRNA可能与64种circRNA结合。总之,这些发现为AD发病机制提供了新的视角,检测到的lncRNA、mRNA和circRNA可能成为AD治疗的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261f/10433443/2db01966dbc7/etm-26-03-12125-g00.jpg

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