We present the results of a global study of dysregulated miRNAs in paired samples of normal mucosa and tumor from eight patients with colorectal cancer.
Although there is existing data of miRNAs contributing to colorectal tumorigenesis, these studies are typically small to medium scale studies of cell lines or non-paired tumor samples. The present study is to our knowledge unique in two respects. Firstly, the normal and adjacent tumor tissue samples are paired, thus taking into account the baseline differences between individuals when testing for differential expression. Secondly, we use high-throughput sequencing, thus enabling a comprehensive survey of all miRNAs expressed in the tissues. We use Illumina sequencing technology to perform sequencing and two different tools to test for differences in read counts per gene between samples: DESeq for pooled sample testing and edgeR for paired sample testing.
We identify 37 miRNAs that are significantly dysregulated in both statistical approaches. 19 down-regulated and 18 upregulated. Some of these miRNAs are previously published as potential regulators in colorectal adenocarcinomas such as miR-1, miR-96 and miR-145. Our comprehensive survey of differentially expressed miRNAs thus confirms some existing findings. We have also discovered 16 dysregulated miRNAs which to our knowledge have not previously been associated with colorectal carcinogenesis. These results add to the present knowledge on miRNA dysregulation in colorectal carcinogenesis by identifying molecules that may either be important regulators of this cancer or be useful as biomarkers. Finally, we also present data supporting the hypothesis that there are differences in miRNA expression between adenocarcinomas and neuroendocrine tumors of the colon.