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Iranian Journal of Public Health، جلد ۵۲، شماره ۵، صفحات ۱۰۱۹-۱۰۳۰
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عنوان انگلیسی Identification of Lncrna-Mrna Networks in Hepg2 Cells upon ATP7B Knockout and Copper Accumulation
چکیده انگلیسی مقاله Background: Hepatolenticular degeneration (HLD) is an inherited disorder caused by the mutation in the adenosine triphosphatase copper transporting β gene (ATP7B). W aimed to explore the genetic changes in HLD using bioinformatics analysis. Methods: The study was conducted in Nepal, in 2019. The GSE107323 dataset was downloaded and the differentially expressed lncRNAs (DElncRNAs) as well as differentially expressed genes (DEGs) induced by ATP7B knockout (KO) and copper toxicity were clustered using Mfuzz clustering analysis. LncRNAs and genes with high coexpression (correlation coefficient > 0.9) and pathways involving the DEGs were used to construct the lncRNA-gene-pathway network. Results: ATP7B KO and ATP7B KO + copper induced 51 overlapping DEGs and 687 overlapping DElncRNAs, respectively. Mfuzz analysis identified four clusters, including two clusters of consistently upregulated and downregulated DEGs/DElncRNAs. The lncRNA-gene-pathway network consisted of 13 DElncRNAs, 10 DEGs, and two pathways, including “hsa04630: Jak-STAT signaling pathway” and “hsa04920: Adipocytokine signaling pathway”. Eight downregulated genes, including erythropoietin (EPO), insulin receptor substrate 1 (IRS1), and PPARG coactivator 1 alpha (PPARGC1A), and two upregulated genes (cardiotrophin-like cytokine factor 1 and cyclin D3) were involved in the two pathways. These genes were targeted by multiple lncRNAs, including PCAT6 and MALAT1. Conclusion: Collectively, the differentially expressed lncRNA-mRNA axes play crucial roles in HLD pathogenesis through mediating cell proliferation and inflammation. Moreover, the EPO, IRS1, or PPARGC1A genes were potent therapeutic targets for HLD.  
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نویسندگان مقاله | Yan Yan
Affiliated Hospital of the Institute of Neurology, Anhui University of Chinese Medicine, Hefei, 230061, P.R. China


| Yin Xu
Affiliated Hospital of the Institute of Neurology, Anhui University of Chinese Medicine, Hefei, 230061, P.R. China


| Lin Chen
Affiliated Hospital of the Institute of Neurology, Anhui University of Chinese Medicine, Hefei, 230061, P.R. China


| Yongzhu Han
Affiliated Hospital of the Institute of Neurology, Anhui University of Chinese Medicine, Hefei, 230061, P.R. China


| Renmin Yang
Affiliated Hospital of the Institute of Neurology, Anhui University of Chinese Medicine, Hefei, 230061, P.R. China


| Wenbin Hu
Affiliated Hospital of the Institute of Neurology, Anhui University of Chinese Medicine, Hefei, 230061, P.R. China
نشانی اینترنتی https://ijph.tums.ac.ir/index.php/ijph/article/view/30527
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