Downregulation of microRNA-1 and microRNA-145 contributes synergistically to the development of colon cancer.

The aim of the present study was to identify the differentially expressed microRNAs (miRNAs or miRs) in patients with colon cancer and examine their roles in the pathogenesis of the disease. The expression profiles of miRNAs were examined in tumor tissue samples collected from 20 patients with histologically confirmed colon cancer and in the adjacent non-cancerous control tissues using microarray analysis. We found that numerous miRNAs were differentially expressed in the colon cancer tissues compared with the control tissues. Following functional analysis, we noted that three miRNAs which were significantly downregulated, miR-145, miR-451 and miR-1, shared the same target gene, [NLR family, apoptosis inhibitory protein (NAIP)], which has previously been reported to be involved in the development of colon cancer. We then confirmed that NAIP is a target gene of miR-145 and miR-1, but not of miR-451, using a luceriferase assay, and we confirmed the expression patterns of these miRNAs and NAIP in the tumor tissue, as well as in the adjacent non-cancerous control tissues. Additionally, in order to examine the function of miR-145 and miR-1 in human colon cancer, we transiently transfected a human colon cancer cell line with miR-145 and miR-1 mimics or inhibitors, and the results of MTT assay revealed that the re-expression of miR-145 and miR-1 inhibited the survival of colon cancer cells, which may be attributed to the inhibition of the anti-apoptotic activity of NAIP. Our findings demonstrated that miR-145 and miR-1 play a negative regulatory role in the proliferation of colon cancer by targeting NAIP; thus, miR-145 and miR-1 may prove to be novel therapeutic targets in the treatment of colon cancer.