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创伤后癫痫大鼠钙通道相关 mRNA 和 miRNA 网络的初步研究。

A preliminary study of calcium channel-associated mRNA and miRNA networks in post-traumatic epileptic rats.

机构信息

Key Laboratory of Evidence Science (China University of Political Science and Law), Ministry of Education, No. 25 Xitucheng Road, Haidian District, Beijing, 100088, China.

Collaborative Innovation Center of Judicial Civilization, Beijing, 100088, China.

出版信息

Sci Rep. 2023 Aug 11;13(1):13103. doi: 10.1038/s41598-023-39485-9.

Abstract

The calcium channels are the main pathogenesis and therapeutic target for post-traumatic epilepsy (PTE). However, differentially expressed miRNAs (DEMs) and mRNAs associated with calcium channels in PTE and their interactions are poorly understood. We produced a PTE model in rats and conducted RNA-seq in PTE rats. Gene annotation was used to verify differentially expressed mRNAs related to calcium channels. RNAhybrid, PITA, and Miranda prediction were used to build the miRNA-mRNA pairs. Furthermore, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used for the functional enrichment analysis of DEMs. The quantification changes of mRNA and miRNA were verified by RT-qPCR. There were 431 identified differentially expressed genes (DEGs) in PTE rats compared with the sham group, of which five mRNAs and 7 miRNAs were related to calcium channels. The miRNA-mRNA network suggested a negative correlation between 11 pairs of miRNA-mRNA involved in the p53 signaling pathway, HIF-1 signaling pathway. RT-qPCR verified three upregulated mRNAs in PTE rats, associated with 7 DEMs negatively related to them, respectively. This study has revealed the changes in miRNA-mRNA pairs associated with calcium channels in PTE, which might contribute to the further interpretation of potential underlying molecular mechanisms of PTE and the discovery of promising diagnostics.

摘要

钙通道是创伤后癫痫(PTE)的主要发病机制和治疗靶点。然而,与 PTE 中钙通道相关的差异表达 miRNA(DEMs)和 mRNAs 及其相互作用尚不清楚。我们在大鼠中产生了 PTE 模型,并对 PTE 大鼠进行了 RNA-seq。使用基因注释来验证与钙通道相关的差异表达 mRNAs。使用 RNAhybrid、PITA 和 Miranda 预测来构建 miRNA-mRNA 对。此外,进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析,以对 DEMs 的功能进行富集分析。通过 RT-qPCR 验证了 mRNA 和 miRNA 的定量变化。与假手术组相比,PTE 大鼠中鉴定出 431 个差异表达基因(DEGs),其中 5 个 mRNAs 和 7 个 miRNAs 与钙通道有关。miRNA-mRNA 网络表明,p53 信号通路和 HIF-1 信号通路中涉及的 11 对 miRNA-mRNA 之间存在负相关。RT-qPCR 验证了 PTE 大鼠中 3 个上调的 mRNAs,它们分别与 7 个与它们负相关的 DEMs 相关。本研究揭示了 PTE 中与钙通道相关的 miRNA-mRNA 对的变化,这可能有助于进一步解释 PTE 的潜在分子机制,并发现有希望的诊断方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99dd/10421957/84d7e0575b74/41598_2023_39485_Fig1_HTML.jpg

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