Golestan University of Medical Sciences Repository

Expression, Tissue Distribution and Function of miR-21 in Esophageal Squamous Cell Carcinoma

Nouraee, N. and Van Roosbroeck, K. and Vasei, M. and Semnani, S. and Samaei, N.M. and Naghshvar, F. and Omidi, A.A. and Calin, G.A. and Mowla, S.J. (2013) Expression, Tissue Distribution and Function of miR-21 in Esophageal Squamous Cell Carcinoma. PLoS ONE, 8 (9). ISSN 19326203 (ISSN)

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Abstract

Objective: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.Design: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.Results: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<0.0001). In addition, co-culturing cancer cells with fibroblasts and expression of miR-21 induced the expression of the cancer associated fibroblast (CAF) marker S100A4.Conclusions:MiR-21 expression is mostly confined to the SCC stroma and its release from fibroblasts influences the migration and invasion capacity of SCC cells. Moreover, miR-21 may be an important factor in "activating" fibroblasts to CAFs. These findings provide new insights into the role of CAFs and the extracellular matrix in tumor microenvironment formation and in tumor cell maintenance, and suggest miR-21 may contribute to cellular crosstalk in the tumor microenvironment. © 2013 Nouraee et al.

Item Type: Article
Additional Information: Unmapped bibliographic data: C7 - e73009 [EPrints field already has value set] LA - English [Field not mapped to EPrints] J2 - PLoS ONE [Field not mapped to EPrints] C2 - 24039846 [Field not mapped to EPrints] AD - Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran [Field not mapped to EPrints] AD - Department of Experimental Therapeutics, MD Anderson Cancer Center, University of Texas, Houston, TX, United States [Field not mapped to EPrints] AD - Pathology Laboratory, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran [Field not mapped to EPrints] AD - Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran [Field not mapped to EPrints] AD - Human Genetics Department, Golestan University of Medical Sciences, Gorgan, Iran [Field not mapped to EPrints] AD - Department of Pathology, Mazandaran University of Medical Sciences, Sari, Iran [Field not mapped to EPrints] AD - Department of Pathology, Mashhad University of Medical Sciences, Mashhad, Iran [Field not mapped to EPrints] DB - Scopus [Field not mapped to EPrints]
Uncontrolled Keywords: collagen type 4, microRNA 21, protein COL4A1, tissue inhibitor of metalloproteinase 4, unclassified drug, article, cancer cell, cancer grading, carcinogenesis, cell invasion, cell migration, controlled study, cytoplasm, esophageal squamous cell carcinoma, fibroblast, gene expression, gene function, gene location, human, human cell, human tissue, protein expression, protein function, tissue distribution, tumor microenvironment, upregulation, Biological Markers, Carcinoma, Squamous Cell, Cell Line, Tumor, Cell Movement, Coculture Techniques, Collagen Type IV, Culture Media, Conditioned, Esophageal Neoplasms, Fibroblasts, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, MicroRNAs, Neoplasm Grading, Organ Specificity, Tissue Inhibitor of Metalloproteinase-3, Up-Regulation
Subjects: مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
موارد کلی
Divisions: معاونت تحقیقات و فناوری
Depositing User: GOUMS
Date Deposited: 15 Apr 2015 04:09
Last Modified: 10 May 2015 10:25
URI: http://eprints.goums.ac.ir/id/eprint/1835

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