(C) The Venn diagram represents the common and differentially expressed genes for the MCPyV (MCV) data set from this study and the studies of Berrios et al
(C) The Venn diagram represents the common and differentially expressed genes for the MCPyV (MCV) data set from this study and the studies of Berrios et al. or MCC cells resulted in a decrease in the number of cells in S phase and cell proliferation inhibition. Moreover, a decrease in wound healing capacity in hTERT-MCPyV gene-expressing HK was observed. Further analysis revealed that NDRG1 exerts its biological effect in Merkel cell lines by regulating the expression of the cyclin-dependent kinase 2 (CDK2) and cyclin D1 proteins. Overall, NDRG1 plays an important role in MCPyV-induced cellular proliferation. IMPORTANCE Merkel cell carcinoma was first described in 1972 as a neuroendocrine tumor of skin, most cases of which were reported in 2008 to be laxogenin caused by a PyV named Merkel cell polyomavirus (MCPyV), the first PyV linked to human cancer. Thereafter, numerous studies have been conducted to understand the etiology of this virus-induced carcinogenesis. However, it is still a new field, and much work is needed to understand the molecular pathogenesis of MCC. In the current work, we sought to identify the host genes specifically deregulated by MCPyV, as opposed to other PyVs, in order to better understand the relevance of the genes analyzed on the biological impact and progression of the disease. These findings open newer avenues for targeted drug therapies, thereby providing hope for the management of patients suffering from this highly aggressive cancer. laxogenin value and FDR of 0.001 for each class are represented in the graph. The numbers on the top of each bar show the total number of up- and downregulated genes by early genes of each PyV. (C) The Venn diagram represents the common and differentially expressed genes for the MCPyV (MCV) data set from this study and the studies of Berrios et al. (25), Masterson et laxogenin al. (26), and Daily et al. (27). The number 1 in the middle indicates the gene (HIST1C1) that was commonly deregulated in the 4 data sets. (D) Cluster F3 analysis of differentially expressed genes involved in cell cycle regulation. The heat maps obtained from BioCarta show the differential laxogenin expression of 28 genes involved in the cell cycle at the G1/S checkpoint (left) or the 23 genes related to cyclins and cell cycle regulation (right) between MCPyV and pLXSN. Color intensities reflect the fold change in expression relative to that in the control cells. Blue and brown show down- and upregulation, respectively. Subsequently, we compared the expression laxogenin profile data for each PyV with the expression profile data for the negative control, i.e., NIKs transduced with an empty retrovirus (pLXSN). The expression of genes is provided as the ratios of the values obtained relative to the values obtained under the control condition after normalization of the data. For comparison between these classes, genes were considered differentially expressed when they displayed a difference of at least a 1.5-fold increase or decrease in expression pattern in both replicates with a value and a false discovery rate (FDR) of 0.001. Using these selection criteria, we identified numerous genes deregulated by each PyV upon comparison with the negative control (Fig. 1B). Notably, most of the genes were downregulated in each class comparison. The exception was the WUPyV genes, for which the number of upregulated genes was higher than the number of downregulated ones. However, SV40 scored a maximum for the deregulation of genes (axis show the number of genes, while the numbers on the axis represent the number of samples. The color bar at the bottom represents the fold change scale, varying from ?2.4 (blue, downregulated) to 2.3 (red, upregulated). (C and D) The 23 genes of the MCPyV-specific signature compared to the SV40-specific (C) and BKPyV-specific (D) signatures. (E) The bar diagram shows the number of genes involved in biological (left) and molecular (right) functions. Using Gene Ontology software, the 28 genes representing the specific signature of MCPyV were analyzed for their.