Abstract

Abstract The mechanisms that regulate microRNA expression in cancer are not fully understood. However, recently reported data show that the epigenetic mechanism plays an important role in the regulation of microRNA expression. In in this study, we investigated the relationship between miR-124 promoter methylation and target genes in CRC. The expression of miR-124 was increased by Aza treatment and the expression of KITENIN was decreased in CRC cells. First, we examined the methylation status of miR-124 promoter in two normal cell lines and seven CRC cell lines using pyrosequencing assay. As a result, miR-124 promoter was hypermethylated in CRC cells and low in normal cells. Next, we evaluated the DNA methylation status for a miR-124 promoter in paired colorectal normal tissues and colorectal cancer tissues specimens from 10 patients. Overall, methylation of the miR-124 promoter was high in cancer among clinical tissues, and the expression of miR-124 was low in cancer tissues. The expression of the KITENIN was also higher in cancer tissues than in normal tissues. These results prove that DNA hypermethylation contributes to the transcriptional down-regulation of miR-124 in colon cancer, and that the epigenetic silencing of miR-124 in cancer cells modulate the activity of KITENIN. Our findings provide basic data that can be useful for clinical treatment of CRC patients through the mechanism of miR-124 regulation identified as a regulator of KITENIN. Citation Format: So-Yeon Park, Rui Zhou, Chathurika D. B. Gamage, Sultan Pulat, Mücahit Varlı, Hangun Kim. Regulation of miR-124 expression by promoter methylation in CRC and its relationship with KITENIN expression. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3793.

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