Expression of DNA methyltransferases and target microRNAs in human tissue samples related to sporadic colorectal cancer.

Tissue microenvironment functions as a pivotal mediator in colorectal carcinogenesis, and its alteration can cause some important cellular responses including epigenetic events. The present study examined histologically altered tissue structure, DNA methyltransferases (DNMTs) and their corresponding expression of target microRNAs (miRNA). Tissues resected by surgery were from primary colorectal carcinoma. These samples were from three locations: and were ≥10, 5 and ≤2 cm away from the proximal lesion of colon cancer, and marked as no. 1, no. 2 and no. 3, respectively. Histological alteration was assessed by H&E staining, expression of DNMT1, DNMT3A, and DNMT3B was detected by immunohistochemistry and western blotting, microarray chip was used to screen distinguishable miRNAs and miRNAs targeting DNMTs whose validation assay was performed by quantitative real-time polymerase chain reaction (qRT-PCR). Our results revealed that normal crypt structure was shown in no. 1, while many aberrant crypt foci appeared in no. 3. Significant upregulation of DNMT1, DNMT3A, and DNMT3B expression was found in para-carcinoma tissues, compared with the histopathologically unchanged tissues (P<0.05), furthermore, distinguishable expression profiling was observed of target miRNAs in tissues with different distance. Our results provide additional insights for future research of colorectal carcinogenesis by introducing the tissue microenvironment.