Exploring CK2 transcriptional regulation and signaling pathways in cancer.

Abstract

e15199 Background: CK2 genes have been implicated in oncogenic processes in different cancer types, and their expression is known to be increased in many cancers relative to their normal tissue types. However the regulation of the three CK2 alpha transcripts and beta transcript is not well understood. Studies investigating the alpha gene ( CSNK2A1) and beta gene ( CSNK2B) found NFκB, ETS1, and SP1 as likely transcription factor regulators in lymphoid and fibroblast cell lines. Our study seeks to explore correlations between CK2 gene expression and the expression of these transcription factors in cancer. Since CK2 also regulates intracellular signaling through pathways such as PI3K-Akt, Jak-Stat, NFkB, Wnt, IL-6, TGF-β, Ras and Notch, this study also seeks to explore the correlation between CK2 expression and gene expression of known downstream signaling pathways across a variety of cancers. Methods: 32 non-overlapping cancer datasets were obtained from the The Cancer Genome Atlas (TCGA) and Broad GDAC Firehose projects which were obtained via cBioPortal.org and analyzed using a combination of cBioportal and RStudio statistical analysis packages. For each cancer type, mRNA expression of each of the four CK2 genes in cancer was compared to expression of transcription factors both previously identified in the literature and predicted generated by TFBIND analysis (via the transcription factor database TRANSFAC R3.4) of the CK2 minimal promoter regions. CK2 gene expression was also compared to expression of genes in known CK2 signaling pathways. Results: Our analysis found CSNK2A1 and CSNK2A3 expression to have a significant, strong positive correlation in nearly all cancer types studied, except pancreatic adenocarcinoma. CSNK2A1 demonstrated significant positive correlation with expression of the transcription factors NFKB1 and c-Rel in lymphoma, thymoma, and other cancers. CSNK2B demonstrated a significant, strong positive correlation with the transcription factors NELFE in every cancer examined. CK2 transcripts also showed significant correlations with other transcription factors and genes involved in IL-6, TGF-β, MAPK, and several other CK2 signaling pathways in many different cancer types. Conclusions: Overall this study demonstrates significant correlations between CK2 gene expression and previously proposed transcriptional regulation mechanisms as well as known CK2 signaling pathways in cancer.