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

Mol Biol Rep. 2024 Nov 4;51(1):1119. doi: 10.1007/s11033-024-10060-3.

ABSTRACT

OBJECTIVE: Colorectal cancer (CRC) is a diverse and multifaceted disease characterized by genetic and epigenetic changes that contribute to tumor initiation and progression. CRC pathophysiology has been linked to the deregulation of the Wnt signaling pathway and the ten-eleven translocation (TET) DNA demethylases. This study aimed to evaluate 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.

MATERIALS AND METHODS: In this study, we assessed TET1 and Wnt1 expression 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 miR-200, miR-494, TET1, and Wnt1 mRNA levels in colorectal polyps, actual colorectal tumors, and normal adjacent tissues.

RESULTS: Our study revealed that TET1 expression was notably lower in both polyps and CRC tissue compared to adjacent normal tissue, with higher TET1 expression in tumors than polyps. We also observed significant differences in miR-200 and miR-494 expression in tumor samples compared to adjacent normal tissue. Our in vitro experiments revealed that 5-azacytidine administration increased TET1 and decreased Wnt1 expression in CRC cell lines. This suggests that DNA-demethylating drugs may have a therapeutic role in modifying TET1 and Wnt signaling in the development of CRC.

CONCLUSIONS: Overall, our findings shed light on the intricate interactions between TET1, Wnt1, and specific miRNAs in colorectal cancer (CRC) and their potential implications for diagnosis and treatment.

PMID:39495308 | PMC:PMC11535070 | DOI:10.1007/s11033-024-10060-3