The genetic and epigenetic regulation of CD55 and its pathway analysis in colon cancer

Background: CD55 played an important role in the development of colon cancer. This study aims to evaluate the expression of CD55 in colon cancer and discover how it was regulated by transcriptional factor and miRNA. Methods The expression of CD55 was explored by Tumor Immune Estimation Resource2.0 (TIMER 2.0), Human Protein Altas (HPA), and UALCAN databases. TRANSFAC and Contra v3 programs were used to predict the potential binding transcription factors in the CD55 promoter. TargetScan and Starbase v2.0 were used to predict potential binding ability of miRNAs to the 3’ untranslated region (3’UTR) of CD55 . SurvivalMeth was used to explore the differentially methylated sites of CD55 promoter in colon cancer. Dual-luciferase reporter assay was performed to determine the targeting relationship of TFCP2, NF-κB, or miR-27a-3p with CD55 . CD55 related genes was explored by constructing a protein-protein interaction (PPI) network. The pathway analysis was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Results CD55 was significantly highly expressed in colon cancer tissues when compared with that in adjacent normal colon tissues. Dual luciferase reporter assays for CD55 promoter region showed that after knocking down TFCP2, the relative luciferase activity was decreased by 21% ( P  < 0.05); after inhibiting NF-κB, the relative luciferase activity was decreased by 70% ( P  < 0.01). The reporter gene activity assay presented that luciferase activity affected by 3’UTR of CD55 was decreased by 46% in the presence of targeting miR-27a-3p ( P  < 0.001). PPI network assay revealed a set of CD55 -related genes, which including CFP, CFB, C4A, C4B, C5AR1, C3, C3AR1, C2, EGF, LCK, CD59, PIGA, PGAP1, ICAM1, EMR2 and CD97. GO and KEGG analysis revealed that the target genes occurred more frequently in immune-related pathways. Conclusion Our results indicated that CD55 was regulated by TFCP2, NF-κB, miR-27a-3p and several immune-related genes, which in turn affects colon cancer.