Expression, tissue distribution and function of miR-21 in esophageal squamous cell carcinoma

• Published in: PloS one 2013-09, Vol.8 (9), p.e73009-e73009
• Main Authors: Nouraee, Nazila, Van Roosbroeck, Katrien, Vasei, Mohammad, Semnani, Shahriar, Samaei, Nader Mansour, Naghshvar, Farshad, Omidi, Abbas Ali, Calin, George A, Mowla, Seyed Javad
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Apoptosis; Archives & records; Biomarkers - metabolism; Cancer; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell culture; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Coculture Techniques; Collagen Type IV - genetics; Collagen Type IV - metabolism; Colorectal cancer; Conditioning; Consent; Crosstalk; Culture Media, Conditioned - pharmacology; Cytoplasm; Esophageal cancer; Esophageal Neoplasms - genetics; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - pathology; Esophageal Squamous Cell Carcinoma; Esophagus; Ethics; Extracellular matrix; Fibroblasts; Fibroblasts - metabolism; Fibroblasts - pathology; Formaldehyde; Gene Expression Regulation, Neoplastic; Hepatology; Humans; Immunohistochemistry; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Neoplasm Grading; Organ Specificity - genetics; Paraffin; Pathology; Polymerase chain reaction; S100A4 protein; Squamous cell carcinoma; Stromal cells; Tissue Inhibitor of Metalloproteinase-3 - genetics; Tissue Inhibitor of Metalloproteinase-3 - metabolism; Tissues; Tumor cell lines; Tumorigenesis; Tumors; Up-Regulation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0073009

MiR-21 is an oncomir expressed by malignant cells and/or tumor microenvironment components. In this study we focused on understanding the effects of stromal miR-21 on esophageal malignant cells. MiR-21 expression was evaluated in formalin-fixed paraffin-embedded samples from patients with esophageal squamous-cell carcinoma (SCC) by quantitative RT-PCR. MiR-21 tissue distribution was visualized with in situ hybridization. A co-culture system of normal fibroblasts and esophageal cancer cells was used to determine the effects of fibroblasts on miR-21 expression levels, and on SCC cell migration and invasion. MiR-21 was overexpressed in SCCs, when compared to the adjacent non-tumor tissues (P = 0.0007), and was mainly localized in the cytoplasm of stromal cells adjacent to malignant cells. Accordingly, miR-21 expression was increased in tumors with high versus low stromal content (P = 0.04). When co-cultured with normal fibroblasts, miR-21 expression was elevated in SCC cells (KYSE-30), while its expression was restricted to fibroblasts when co-cultured with adenocarcinoma cells (OE-33 and FLO-1). MiR-21 was detected in conditioned media of cancer cell lines, illustrating the release of this miRNA into the environment. Co-culturing with normal fibroblasts or addition of fibroblast conditioned media caused a significant increase in cell migration and invasion potency of KYSE-30 cells (P