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

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.