| Recent studies suggest a role of the proteasome activator, REGγ, in cancer progression. Currently there are limited numbers of known REGγtargets. Furthermore it is not known which cancers and pathways are associated with REGγ. Data mining of publicly available microarray databases allowed us to carry out computational analysis along with biological studies to explore REGy profiles and functions in different cancer types. In this paper, REGy protein expressions in four different cancers were estimated by immunohistochemistry (IHC). Meta-analysis of 1070 cancer samples was performed to identify genes that correlated with up regulation of REGγin 4 cancer types and 23 datasets available from the Gene Expression Omnibus (GEO). Genes with highly correlated REGy expression were identified based on Pearson's correlation coefficient. Functional links were estimated by pathway analysis. Finally, these correlations were tested by RT-PCR in established cancer cell lines and IHC in human colon cancer tissues. Using the methods and materials above, the following results were disclosed. Enhanced REGγprotein levels were observed in over 50% of lung, colon, thyroid, and liver cancers. Analysis of GEO datasets revealed a similar increase of REGy in all cancer types examined. Significant correlation was observed between REGy and genes in p53 pathway and multiple other cancer-related pathways. The predicted correlations were largely consistent with RT-PCR validation. Network analysis highlighted the link between REGγand Myc, which was further supported by IHC study in human colon cancer. To sum up, we demonstrate elevated REGy expression in multiple cancer types. This study provides us novel insights in REGy gene expression profiles and its link to multiple cancer-related pathways in cancers. Our results indicate potentially important pathogenic roles of REGy in multiple cancer types and implicate REGy as a putative cancer marker.
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