The implication of TET1, miR-200 and miR-494 expression with tumor formation in colorectal cancer: through targeting WNT signaling

Objective: Colorectal cancer (CRC) is a heterogeneous disease characterized by genetic and epigenetic alterations that contribute to tumor initiation and progression. Among these, dysregulation of the ten–eleven translocation (TET) DNA demethylases and the Wnt signaling pathway have been implicated in CRC pathogenesis. This study aimed to assess the expression level of selective miRNAs (miR-200 and miR-494), TET1 and Wnt1 in colorectal polyps, actual colorectal tumors, and normal adjacent tissues. We also evaluated the effect of 5-aza cytidine on the expression level of TET1 and wnt1 in the HT29 cell line. Material and methods: TET1 and Wnt1 expression was assessed in 5-azacytidine-treated HT29 cells, a demethylating agent commonly used in cancer therapy. Additionally, we enrolled 114 individuals who underwent radical surgical colon resection, including 47 with cancerous tissues and 67 with polyps. We utilized qRT-PCR to measure mRNA levels of miR-200, miR-494, TET1 and Wnt1 in colorectal polyps, actual colorectal tumors, and normal adjacent tissues. Results: TET1 expression was notably lower in both polyps and CRC tissue in comparison to adjacent normal tissue, with higher TET1 expression in tumors compared to polyps. Significant differences in miR-200 and miR-494 expression was observed in tumor samples compared to adjacent normal tissue. Furthermore, our in vitro experiments revealed that 5-azacytidine treatment upregulated TET1 and downregulated Wnt1 expression in CRC cell line, suggesting a potential therapeutic role for DNA demethylating agents in modulating TET1 and Wnt signaling in CRC development. Conclusions: Overall, our findings provide further insight into the complex interplay between TET1, Wnt1 and selective miRNAs in CRC and their potential implications for diagnosis and treatment.