Gene expression profile after knockdown of USP18 in Hepg2.2.15 cells

Abstract

In our previous work, we found that the expression of ubiquitin-specific protease 18 (USP18), also known as UBP43, is associated with the efficiency of interferon alpha (IFN-α) treatment in patients with chronic hepatitis B (CHB). To elucidate the influence of USP18 on hepatitis B virus (HBV) replication and the mechanism of this activity, we silenced USP18 by introducing short hairpin RNA (shRNA) into Hepg2.2.15 cells. To identify the changed genes and pathways in Hepg2.2.15-shRNA-USP18 cells, we performed a microarray gene expression analysis to compare the Hepg2.2.15 stably expressing USP18-shRNA cells versus control cells using the Affymetrix Human Transcriptome Array (HTA) 2.0 microarrays. Microarray analysis indicated that genes involved in regulation of thyroid hormone signaling pathway, complement, and coagulation cascades, PERK-mediated unfolded protein response, and insulin-like growth factor-activated receptor activity were significantly altered after USP18 knockdown for 72 h. Furthermore, genes involved in hepatocyte proliferation, liver fibrosis, such as cell cycle regulatory gene CCND1, were also altered after USP18 knockdown in Hepg2.2.15 cells. In conclusion, USP18 is critical for regulating the replication of HBV in Hepg2.2.15 cells, which suggest that USP18 may be a candidate target for HBV treatment.

Comprehensive Analysis of the mRNA-lncRNA Co-expression Profile and ceRNA Networks Patterns in Chronic Hepatitis B

“…Our findings are in accordance with the studies on HBV infection and the immune process, in which the main enrichments were those corresponding to the innate and adaptive immunity responses. Additionally, we evaluated these DEGs by KEGG pathway analysis and identified 19 associated pathways, including the TGF-signaling pathway and complement and coagulation cascades, which are linked with cirrhosis in HBV infection and in hepatocellular carcinoma [31,32]. These results indicated that DGEs participate in HBVmediated progression of CHB to liver cirrhosis and hepatocellular carcinoma.…”

Roles of ubiquitin-specific proteases in inflammatory diseases

“…Additionally, USP18 dampens the effects of type I and type III IFNs by exerting negative feedback control through its regulatory role ( 89 ). Moreover, USP18 also binds to and deubiquitinates TAK1, thereby promoting hepatic inflammatory responses ( 90 – 92 ).…”

Targeting Thyroid Hormone/Thyroid Hormone Receptor Axis: An Attractive Therapy Strategy in Liver Diseases

“…Some studies have demonstrated that ubiquitin-specific protease 18 (USP18), known as UBP43, participates in gene regulations of the TH signaling pathway. Li et al, (2017 ) discovered that USP18 regulates the signaling of antivirus by the TH signaling pathway, prolactin signaling pathway, insulin resistance and complement, and have crosstalk among them. Also, the thyroid hormone-uncoupling protein (TRUP) gene and thyroid hormone receptor-associated protein 150 alpha gene are associated to the integration of HBV DNA into liver cell DNA, which are the key regulators of cell proliferation and viability ( Gozuacik et al, 2001 ; Paterlini-Bréchot et al, 2003 ).…”