Clinical Correlation of miR-200c/141 Cluster DNA Methylation and miR-141 Expression with the Clinicopathological Features of Colorectal Primary Lesions/Tumors

Background: Abnormal DNA methylation leading to altered transcription of certain genes occurs frequently in colorectal cancer (CRC). As with protein-coding genes, microRNAs (miRNAs) may be targeted for methylation in CRC; however, the methylation state of miRNA genes in CRC, especially in primary lesions, has not yet been completely elucidated. To understand the impact of DNA methylation on the miR-200c/141 cluster promoter, we investigated the methylation and expression of miR-141 in precancerous lesions and colorectal cancer. Methods: In this cross-sectional study, 208 colorectal tissue samples, including 34 tumor tissue samples, 60 precancerous lesions with matched normal adjacent tissues, and 20 normal tissue samples, were collected. Promoter methylation of the miR-200c/141 cluster was studied using methylation-specific PCR. MiR-141 expression was examined using quantitative real-time PCR. Results: Our findings showed that the miR-200c/141 cluster promoter region was most frequently hypermethylated in colorectal tumors and adenomatous polyps, but unmethylated in hyperplastic polyp tissues (P < 0.001). DNA methylation of the miR-200c/141 cluster and the tumor stage were significantly correlated (P = 0.002); however, miR-141 expression difference between the tumor and polyp samples was not significant (p = 0.6). Conclusions: The DNA methylation status of the miR-200c/141 cluster could serve as a progression marker from benign polyps to colorectal cancer.

Keywords:

Colonic Polyps , Colorectal Cancer , DNA methylation , MiR-141