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.

The Influence of Spirulina platensis Filtrates on Caco-2 Proliferative Activity and Expression of Apoptosis-Related microRNAs and mRNA

“…The expression of miR-17 and miR-146 was downregulated, while the expression of miR-145 was upregulated. This is consistent with the role of these miRNAs in cancer development—the overexpression of miR-17 and mir-146 is a feature of hyper-proliferating cancer cells [20,59], while the enhanced expression of miR-145 impairs proliferation of the HCT116 colon cancer cell line [60]. …”

Molecular mechanism of myofibroblast formation and strategies for clinical drugs treatments in hypertrophic scars

“…Alao, miR‐4269, miR‐382, miR‐203, miR‐205, miR‐150, and miR‐196a were also considered to influence TGF‐β1 to regulate collagen synthesis (Ferrante et al, ; Zhou et al, ). Besides, miR‐145 targeted Smad3, while miR‐18 and miR‐146a inhibited Smad4 expression (Knudsen et al, ). Smad7 played antagonistic roles in the fibrosis for TGF‐β1 pathway and upregulation of miR‐21 expression could reduce Smad7 expression (Ding et al, ; Wu et al, ; Yang et al, ).…”

Characterization of miRNAs involved in response to poly(I:C) in porcine airway epithelial cells

“…miR‐17‐92 has been involved in a number of malignancies (Knudsen et al . ; Zhu et al . ) and host immune responses during viral infection (Skalsky et al .…”

“…Although transcribed as a polycistron, members of the miR‐17‐92 cluster may play different roles: miR‐17 is the most functional in the cluster during the early evolution of colon cancer (Knudsen et al . ), and three (miR‐19b/20a/92a) instead of all members regulate the self‐renewal of gastric cancer stem cells (Wu et al . ).…”