title: microRNA-17 Is the Most Up-Regulated Member of the miR-17-92 Cluster during Early Colon Cancer Evolution.
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.
authors.affiliation: Department of Clinical Pathology, Vejle Hospital, Part of Lillebaelt Hospital, Vejle, Denmark; Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Kirsten Nguyen
authors.initials: KN
authors.lastname: Knudsen
authors.affiliation: Bioneer A/S, Hørsholm, Denmark.
authors.forename: Boye Schnack
authors.initials: BS
authors.lastname: Nielsen
authors.affiliation: Department of Clinical Pathology, Vejle Hospital, Part of Lillebaelt Hospital, Vejle, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Lindebjerg
authors.affiliation: Department of Oncology, Vejle Hospital, Part of Lillebaelt Hospital, Vejle, Denmark.
authors.forename: Torben Frøstrup
authors.initials: TF
authors.lastname: Hansen
authors.affiliation: Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.
authors.forename: René
authors.initials: R
authors.lastname: Holst
authors.affiliation: Department of Clinical Pathology, Vejle Hospital, Part of Lillebaelt Hospital, Vejle, Denmark; Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Flemming Brandt
authors.initials: FB
authors.lastname: Sørensen
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D057054:Molecular Imaging; D005810:Multigene Family; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D051176:beta Catenin / Q000235:genetics
chemical_list: C524941:MIRN17 microRNA, human; D035683:MicroRNAs; D051176:beta Catenin; D051059:PTEN Phosphohydrolase