The NF-kappa B signalling pathway in colorectal cancer: associations between dysregulated gene and miRNA expression
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
Authors: Slattery, Martha L.; Mullany, Lila E.; Sakoda, Lori; Samowitz, Wade S.; Wolff, Roger K.; Stevens, John R.; Herrick, Jennifer S.
Abstract
Background The nuclear factor-kappa B (NF-kappa B) signalling pathway is a regulator of immune response and inflammation that has been implicated in the carcinogenic process. We examined differentially expressed genes in this pathway and miRNAs to determine associations with colorectal cancer (CRC). Methods We used data from 217 CRC cases to evaluate differences in NF-kappa B signalling pathway gene expression between paired carcinoma and normal mucosa and identify miRNAs that are associated with these genes. Gene expression data from RNA-Seq and miRNA expression data from Agilent Human miRNA Microarray V19.0 were analysed. We evaluated genes most strongly associated and differentially expressed (fold change (FC) of > 1.5 or < 0.67) that were statistically significant after adjustment for multiple comparisons. Results Of the 92 genes evaluated, 22 were significantly downregulated and nine genes were significantly upregulated in all tumours. Two additional genes (CD14 and CSNK2A1) were dysregulated in MSS tumours and two genes (CARD11 and VCAM1) were downregulated and six genes were upregulated (LYN, TICAM2, ICAM1, IL1B, CCL4 and PTGS2) in MSI tumours. Sixteen of the 21 dysregulated genes were associated with 40 miRNAs. There were 76 miRNA:mRNA associations of which 38 had seed-region matches. Genes were associated with multiple miRNAs, with TNFSRF11A (RANK) being associated with 15 miRNAs. Likewise several miRNAs were associated with multiple genes (miR-150-5p with eight genes, miR-195-5p with four genes, miR-203a with five genes, miR-20b-5p with four genes, miR-650 with six genes and miR-92a-3p with five genes). Conclusions Focusing on the genes and their associated miRNAs within the entire signalling pathway provides a comprehensive understanding of this complex pathway as it relates to CRC and offers insight into potential therapeutic agents.
THE HUMAN GENE (CSNK2A1) CODING FOR THE CASEIN KINASE-II SUBUNIT-ALPHA IS LOCATED ON CHROMOSOME-20 AND CONTAINS TANDEMLY ARRANGED ALU REPEATS
GENOMICS
Authors: WIRKNER, U; VOSS, H; LICHTER, P; ANSORGE, W; PYERIN, W
Abstract
We have isolated and characterized a 18.9-kb genomic clone representing a central portion of the human casein kinase II (CKII) subunit alpha gene (CSNK2A1). Using the whole clone as a probe, the gene was localized on chromosome 20p13. The clone contains eight exons whose sequences comprise bases 102 to 824 of the coding region of the human CKII alpha. The exon/intron splice junctions conform to the gt/ag rule. Three of the nine introns are located at positions corresponding to those in the CKII alpha gene of the nematode Caenorhabditis elegans. The introns contain eight complete and eight incomplete Alu repeats. Some of the Alu sequences are arranged in tandems of two or three, which seem to originate from insertions of younger Alu sequences into the poly(A) region of previously integrated Alu sequences, as indicated by flanking direct repeats. (C) 1994 Academic Press, Inc.