Abstract
Deregulated microRNAs play a role in the development and progression of colon cancer, but little is known about their tissue and cell distribution in the continuum of normal mucosa through the premalignant adenoma to invasive adenocarcinoma. The aim of this study was to examine the expression pattern of the miR-17-92 cluster (miR-17, miR-18, miR-19, miR-20 and miR-92) as well as miR-21, miR-31, miR-135b, and miR-145 in early clinically diagnosed colon cancer. MicroRNAs were analysed by chromogenic in situ hybridisation in the normal-adenoma-adenocarcinoma sequence of nine adenocarcinomas developed in mucosal colon polyps. Subsequently, the expression of selected microRNAs was validated in 24 mucosal colon cancer polyps. Expression of miR-17 was confined to the epithelial cells, and the expression levels increased in the transitional zone from normal to adenomatous tissue. The miR-17-92 cluster members, miR-19b, miR-20a, and miR-92a, followed the same expression pattern, but miR-17 was the most predominant. An increased expression of miR-21 was found in the tumour-associated stroma with the most dramatic increase from adenoma to adenocarcinoma, while the number of positive miR-145 fibroblast-like cells in the normal lamina propria (stroma) decreased in a stepwise manner throughout the normal-adenoma-adenocarcinoma sequence. It is concluded that the expression of miR-17, miR-21, and miR-145 changes at early stages of the normal-adenoma-adenocarcinoma sequence. Thus, these microRNAs may play a role in the development of colon cancer.
Highlights
IntroductionA considerable fraction of these cancers are believed to develop in a stepwise manner from normal colonic mucosa through a premalignant adenoma to the invasive adenocarcinoma as a result of complex genetic and epigenetic changes[2,3,4]
Colorectal cancer is among one of the most common cancers worldwide[1]
All cases showed strong expression of miR-145 seen in the smooth muscle cells (SMC) and vascular smooth muscle cells (VSMC) as well as in fibroblast-like stromal cells
Summary
A considerable fraction of these cancers are believed to develop in a stepwise manner from normal colonic mucosa through a premalignant adenoma to the invasive adenocarcinoma as a result of complex genetic and epigenetic changes[2,3,4]. MicroRNAs (miRNAs) are a class of non-coding RNA mediating post-transcriptional regulation that have been implicated in colorectal. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funder provided support in form of salary, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript
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