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长链非编码RNA介导的竞争性内源RNA网络揭示了扫日劳-4汤抗肺纤维化的作用机制。

LncRNA-mediated ceRNA network reveals the mechanism of action of Saorilao-4 decoction against pulmonary fibrosis.

作者信息

Fu Xinyue, Song Xinni, Niu Shufang, Shi Songli, Chang Hong, Qi Jun, Wang Peng, Bai Wanfu

机构信息

Department of Pharmacy, Baotou Medical College, Baotou, China.

The First Affiliated Hospital of Baotou Medical College, Baotou, China.

出版信息

Front Genet. 2024 Mar 12;15:1339064. doi: 10.3389/fgene.2024.1339064. eCollection 2024.

Abstract

Pulmonary fibrosis (PF), a type of interstitial pneumonia with complex etiology and high mortality, is characterized by progressive scarring of the alveolar interstitium and myofibroblastic lesions. In this study, we screened for potential biomarkers in PF and clarified the role of the lncRNA-miRNA-mRNA ceRNA network in the inhibitory effect of SRL-4 on PF. Healthy male SPF SD rats were randomly divided into three groups, namely, CON, MOD, and SRL-4. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to determine the biological functions of the target genes. A visualized lncRNA-miRNA-mRNA ceRNA network was constructed using Cytoscape, while key genes in the network were identified using the cytoNCA plugin. Seventy-four differentially expressed lncRNAs and 118 differentially expressed mRNAs were identified. Gene Ontology analysis revealed that the target genes were mainly enriched in the cell membrane and in response to organic substances, while Kyoto Encyclopedia of Genes and Genomes analysis showed that the target genes were mainly enriched in the AMPK, PPAR, and cAMP signaling pathways. We elucidated a ceRNA axis, namely, Plcd3-OT1/rno-miR-150-3p/Fkbp5, with potential implications in PF. Key genes, such as AABR07051308.1-201, F2rl2-OT1, and LINC3337, may be important targets for the treatment of PF, while the AMPK, PPAR, and cAMP signaling pathways are potential key targets and important pathways through which SRL-4 mitigates PF. Our findings suggest that SRL-4 improves PF by regulating the lncRNA-miRNA-mRNA network.

摘要

肺纤维化(PF)是一种病因复杂、死亡率高的间质性肺炎,其特征为肺泡间质进行性瘢痕形成和肌成纤维细胞病变。在本研究中,我们筛选了PF中的潜在生物标志物,并阐明了lncRNA-miRNA-mRNA ceRNA网络在SRL-4对PF的抑制作用中的作用。将健康雄性SPF SD大鼠随机分为三组,即对照组(CON)、模型组(MOD)和SRL-4组。进行基因本体论(Gene Ontology)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes)富集分析以确定靶基因的生物学功能。使用Cytoscape构建可视化的lncRNA-miRNA-mRNA ceRNA网络,同时使用cytoNCA插件识别网络中的关键基因。鉴定出74个差异表达的lncRNA和118个差异表达的mRNA。基因本体论分析显示靶基因主要富集于细胞膜和对有机物质的反应,而京都基因与基因组百科全书分析表明靶基因主要富集于AMPK、PPAR和cAMP信号通路。我们阐明了一条ceRNA轴,即Plcd3-OT1/rno-miR-150-3p/Fkbp5,其在PF中可能具有潜在意义。关键基因,如AABR07051308.1-201、F2rl2-OT1和LINC3337,可能是PF治疗的重要靶点,而AMPK、PPAR和cAMP信号通路是SRL-4减轻PF的潜在关键靶点和重要途径。我们的研究结果表明,SRL-4通过调节lncRNA-miRNA-mRNA网络改善PF。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c14/10963618/9193bd42f865/fgene-15-1339064-g001.jpg

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