Nazila Nouraee - Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
Mohamad Vasei - Pathology laboratory, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
George A. Calin - Department of Experimental Therapeutics, MD Anderson Cancer Center, University of Texas, Houston, Texas, United States of America.
Seyed Javad Mowla - Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

During the past decade, microRNAs have been emerged as a new class of molecular markers in the diagnosis, prognosis, and targeted therapy of various cancers. Recently, detection of miRNAs in the tumor stroma and their contribution to cancer progression has changed the tumor cell-based standpoint of cancer. In this study, we focused on cancer associatedfibroblasts (CAFs), as the main components of tumor stroma. Simulating the tumor microenvironment, we delved into miR-21, miR-205, miR-200c and miR-29a as candidate miRNAs involved in progression of esophageal cancer.Normal human fibroblasts were co-cultured with KYSE-30 cells (squamous cell carcinoma of esophagus). Using qRT-PCR,the expression alterations of miR-21, miR-205 and miR-29a were evaluated in these cell lines, after 1, 2 and 3 days of incubation. Also using qPCR-based profiling method, the miRNA expression alterations were analyzed in the conditioned medium derived from the co-culture system.Over-expression of miR-21, miR-205 and miR-200c was observed in KYSE-30 cell line co-cultured with fibroblast cells.Moreover, the vicinity of fibroblasts to KYSE-30 cells triggered induction of miR-200c in the former cells. Treatment ofthese fibroblasts with the conditioned medium obtained from KYSE-30 cell line led to the expression of miR-21 and miR- 200c. Real-time PCR analysis on the miRNAs present in the conditioned medium derived from both cell lines revealed asignificantly higher secretion of miR-21, miR-205 and miR-29a into the medium by KYSE-30 cell line.Our data provide new insights into the role of microRNAs as important signaling mediators in cellular cross-talks and theeffects of microenvironment and extracellular matrix in tumorigenesis.

microRNAs, tumor microenvironment, cancer associated fibroblasts (CAFs), signaling molecules