A pan-cancer analysis of Dyskeratosis congenita 1 (DKC1) as a prognostic biomarker

Abstract

Abstract Background Dyskeratosis congenita 1 (DKC1), a critical component of telomerase complex, is highly expressed in a variety of human cancers. However, the association of DKC1 with cancer occurrence and development stages is unclear, thus the pan-cancer analysis appears essential. Methods Though bioinformatic databases including TIMER, GEPIA, UALCAN and KM plotter Analysis, we studied the different expression of DKC1 in multiple tissues and the correlation of DKC1 expression with pathological stages. The DKC1-associated genes and signaling pathways were revealed though KEGG analysis, GO enrichment analysis and Venn analysis. Moreover, we preformed the CCK, wound healing assay, cell cycle arrest assay, transwell assay and Sa-β-gal staining in DKC1-deleted MDA-231 cells. Results Our study shows that DKC1 has relatively low expression specificity in different tissues. Moreover, in ACC, KICH, KIRP and LIHC, the DKC1 expression level is correlated with the pathological stages positively. In addition, in NHSC, KIRP, LGG, LIHC, MESO and SARC, a negative influence of DKC1 expression level on overall survival rate was detected. DKC1 expression and Tumor Mutational Burn were significantly positively correlated in 14 tumors. In the case of BRCA, a significantly negative influence of DKC1 DNA methylation on gene expression was found at the promoter region. We also found plenty of phosphorylation sites concentrated at the C-terminus of the DKC1 protein. With the GO analysis, DKC1 and ribosomal biosynthesis pathways are correlated, and the common element UTP14A is revealed. Moreover, decreased rates of cell proliferation, migration and invasion abilities were found in DKC1 knockout MDA-MB-231 cell lines. DKC1-knockout also arrested cell cycle and caused cell senescence. Conclusions The accurate expression of DKC1 is highly related with the pathological occurrence and development stages in multiple tissues. The depletion of DKC1 inhibits the proliferation, migration and invasion abilities of cancer cells by inhibiting cell cycle then causing cell senescense. This showed that DKC1 can serve as a prognostic biomarker for the diagnosis and treatment of cancer in different tissues.