functions as a potential novel oncopromoter in colorectal cancer: a comprehensive analysis of the gene family.

Pre-B-cell leukaemia (PBX) is a transcription factor family ( and ) that regulates important cellular functions and has been identified to be involved in human cancers. This study aimed to explore the expression of genes and their clinical significance in colorectal cancer (CRC). We analysed the differential expression of genes in CRC vs. normal tissue, using the Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/) and ONCOMINE platform (https://www.oncomine.org/). The UALCAN (http://ualcan.path.uab.edu/) interactive OMICS web-server was used to evaluate the epigenetic regulation of genes via their promoter methylation status. We found that only was upregulated whereas and were downregulated (644 tumour vs. 51 normal samples) (P<0.001). The methylation status of promoter appeared to be decreased (P=1.4e-07) whereas the methylation status of and promoters was increased (P=3.8e-04 and P=3.2e-07, respectively) in cancer vs. normal samples. To determine the prognostic value of , we conducted a Kaplan-Meier survival analysis and multivariable COX regression. We observed that high expression was associated with increased risk for a worse overall survival (OS) in the TCGA CRC patient cohort (n=639), (HR 1.46, 95% CI 1.14-1.88, P=0.003) adjusted for age, gender, tumour location and metastases. We conducted in vitro gene expression modulation experiments to investigate the impact of overexpression in CRC cell (HCT116) growth. Additionally, we evaluated the RNA expression of epithelial-mesenchymal transition (EMT) and angiogenesis markers. studies showed that overexpression increased CRC cell proliferation (P<0.001) and upregulated the expression of EMT markers (P<0.05) and angiomarker (P<0.0001). Lastly, through the Cistrome data browser (http://dbtoolkit.cistrome.org/) we investigated putative transcriptional regulators and we performed gene set enrichment analysis in Enrichr server (https://maayanlab.cloud/Enrichr/) to identify related biological processes. Nineteen factors were identified to be putative regulators of and gene set enrichment analysis showed that biological processes related to cell cycle and cell proliferation were enriched (GO:0051726: , and , P=0.001). In conclusion, our study identified as a potential novel oncopromoter in CRC and its overexpression was found to be associated with increased risk for worse survival rate.