Differentially expressed lncRNAs in liver tissues of TX mice with hepatolenticular degeneration

Abstract

Wilson's Disease (WD), an ATP7B-mutated inherited disease that affects copper transport, is characterised by liver and nervous system manifestations. Long non-coding (ln-c) RNAs are widely involved in almost all physiological and pathological processes in the body, and are associated with numerous diseases. The present study aimed to elucidate the lncRNA-mRNA regulation network in a TX WD mouse model using RNA sequencing (RNA-seq). lncRNA expression profiles were screened using RNA-seq and real-time polymerase chain reaction, and differentially expressed lncRNAs and mRNAs were identified. To analyse the biological functions and pathways for the differentially expressed mRNAs, gene ontology and pathway enrichment analyses were performed. A significantly correlated lncRNA-mRNA relationship pair was calculated by CNC analysis to construct differential lncRNA and mRNA co-expression networks. A total of 2564 significantly up-regulated and 1052 down-regulated lncRNAs, and 1576 up-regulated and 297 down-regulated mRNAs, were identified. These genes were found to be associated with key processes such as apoptosis, and KEGG analysis revealed enrichment in the drug metabolism-cytochrome P450 pathway, PPAR signalling pathway, Notch signalling pathway, and MAPK signalling pathway. The identified differential lncRNAs may be involved in the pathogenesis and development of WD liver injury.

A grading method for Kayser Fleischer ring images based on ResNet

“…Hepatolenticular degeneration (HLD) is also known as Wilson's Disease (WD) [ 1 ]. It is characterized by copper accumulation in different tissues and organs such as the liver, nervous system, kidney, and eyes [ 2 ].…”

Wilson Disease: Update on Pathophysiology and Treatment

“…The metabolomic analysis of WD patients’ serum suggested existence of distinct metabolic profiles differentiating WD from other liver disorders as well as WD with different phenotypic manifestations ( Sarode et al, 2019 ; Azbukina et al, 2020 ). The contribution of miRNA and long non-coding RNA to pathogenesis of WD appears likely ( Zhang et al, 2021 ), but remains understudied. Significant gender-related differences in Cu levels, metabolic, and fibroinflammatory changes are observed in human WD and WD mouse models emphasizing the importance of including both sexes in testing new therapeutic approaches ( Litwin et al, 2012 ; Li et al, 2018 ; Gottlieb et al, 2022 ).…”

Cuproptosis-related long non-coding RNAs model that effectively predicts prognosis in hepatocellular carcinoma

“…Similarly, lncRNAs have been reported to have crucial roles in the regulation of metabolism of metal ion homeostasis. Some 2564 LncRNAs were found to be significantly upregulated, whereas 1052 were downregulated, in a recently constructed toxic milk mouse model of Wilson’s disease (WD), which is characterized by a mutation of the ATP7B gene that affects copper transport[ 14 ]. The cytosolic lncRNA P53RRA was found to displace p53 from the G3BP1-p53 complex, resulting in increased intranuclear p53 retention and manifestation of ferroptosis, another ion-induced form of programmed cell death[ 15 ].…”