In this study Oncomine GEO and TCGA
In this study, Oncomine, GEO and TCGA databases were used to analyze the expression of UBE2S gene in HCC and normal liver tissues to determine the relationship between UBE2S expression and prognosis of hepatocellular carcinoma. The potential function of UBE2S in HCC was analyzed by screening UBE2S co-expressed genes using cBioPortal, as well as GO and KEGG analyses performed using The Database for Annotation, Visualization and Integrated Discovery (DAVID). Finally, the relationship between UBE2S expression and prognosis of HCC was verified by GSEA and qPCR.
Materials and methods
Discussion Previous studies have shown that UBE2S is highly expressed in various human cancers, including esophageal cancer , kidney cancer , breast cancer , among others . Here, we analyzed three datasets in Oncomine database and RNA-seq data from TCGA, and found that UBE2S expression was significantly higher in hepatocellular carcinoma samples. These results were further confirmed by qPCR analysis of UBE2S expression in hepatocellular carcinoma and adjacent cancer samples, suggesting that UBE2S may play a role in the development of HCC. In order to investigate the role of UBE2S in hepatocellular carcinoma, we performed GO and KEGG analyses on UBE2S co-expressed genes and found that UBE2S participated in biological processes including the G1/S transition of mitotic cell cycle, DNA replication, cell proliferation and DNA repair, as well as in signal pathways such including DNA replication and cell cycle. Studies have shown that knockdown of UBE2S expression in oral squamous cell carcinoma can increase the expression of P21, decrease cell growth and induce mtor inhibitor arrest in G2 / M phase . DNA damage in glioblastoma multiform disease has been shown to enhance UBE2S-Ku70 interaction and promote the recruitment of UBE2S to double-strand breaks; recruited UBE2S then participates in NHEJ-mediated DNA repair . These results suggest that UBE2S may have an influence on the cell cycle, DNA replication and DNA repair in the development of HCC. Studies have shown that UBE2S is highly expressed in breast cancer tissue and can promote malignancy of breast cancer cells, specifically migration and invasion . Previous studies have also suggested that UBE2S may play a role in promoting HCC cell metastasis and recurrence, and therefore, influence the prognosis of HCC. We used qPCR to further verify previous bioinformatics analyses. The ROC curve of UBE2S showed that its mRNA expression level has a high diagnostic value in the differentiation between HCC and non-cancerous liver tissue. Consistent with the previous analysis, Kaplan–Meier survival analysis showed that higher expression of UBE2S was significantly associated with decreased overall survival and disease-free survival in HCC patients.
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Introduction Plus-stranded (+)RNA viruses replicate in the infected cells by assembling membrane-bound viral replicase complexes (VRCs), which consist of viral- and host-coded proteins and the viral RNA template. Viral replication proteins of many (+)RNA viruses interact with various subcellular membranes that could result in the formation of spherules, which are single-membrane vesicles with a narrow opening towards the cytosol that harbor VRCs (de Castro et al., 2013, den Boon et al., 2010, Nagy and Pogany, 2012). Although major progress has recently been made in understanding of VRC assembly, the contribution of many host proteins to VRC assembly is far from complete (Belov and van Kuppeveld, 2012, Huang et al., 2012, Mine and Okuno, 2012, Nagy, 2008, Nagy and Pogany, 2008, Nagy and Pogany, 2012, Shulla and Randall, 2012). Postranslation protein modification via addition of the highly conserved ubiquitin to substrate proteins by E1, E2 and E3 enzymes occurs frequently in eukaryotic cells (Popovic et al., 2014, van Wijk and Timmers, 2010). Poly-ubiquitination usually targets the substrate proteins for destruction by the 26S proteasome. Alternatively, ubiquitination, especially mono- and multi-ubiquitination alters the biochemical properties and subcellular localization of substrate proteins (Popovic et al., 2014, van Wijk and Timmers, 2010). Ubiqutination also greatly affects the functions of many viral proteins and viruses actively manipulate the ubiquitin network to suppress innate immunity (Alcaide-Loridan and Jupin, 2012, Lindner, 2007, Okumura et al., 2006, Shackelford and Pagano, 2004, Shackelford and Pagano, 2005, Taylor and Barry, 2006).