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

摘要

Background:Abnormal DNA methylation leading to altered transcription of certain genes occurs frequentlyin colorectal cancer (CRC). As with protein-coding genes, microRNAs (miRNAs) may be targeted formethylation 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/141cluster promoter, we investigated the methylation and expression of miR-141 in precancerous lesions andcolorectal cancer.Methods:In this cross-sectional study, 208 colorectal tissue samples, including 34 tumor tissue samples, 60precancerous 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-141expression was examined using quantitative real-time PCR.Results:Our findings showed that the miR-200c/141 cluster promoter region was most frequently hypermethylatedin colorectal tumors and adenomatous polyps, but unmethylated in hyperplastic polyp tissues (P 0.001). DNAmethylation 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 markerfrom benign polypsto colorectal cancer.