Key result
ATP7B knockout and copper accumulation alters ~738 overlapping genes and lncRNAs in HepG2 cells.
Why the study?
Hepatolenticular degeneration is an inherited disorder caused by mutations in ATP7B, prompting exploration of the underlying genetic changes using bioinformatics analysis.
Differentially expressed lncRNA-mRNA axes, including targets like EPO, IRS1, and PPARGC1A, play crucial roles in Hepatolenticular degeneration pathogenesis.
In vitro transcriptomic changes require validation in patient-derived models; leaves open lncRNA functions in copper-related liver disease.
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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Yan et al. (2023) studied Hepatolenticular degeneration (HLD). ATP7B knockout and copper accumulation was evaluated on Differentially expressed lncRNAs and genes. ATP7B knockout and copper accumulation in HepG2 cells induced 51 overlapping differentially expressed genes and 687 overlapping differentially expressed lncRNAs.
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