ORIGINAL ARTICLE Predicting the molecular role of MEIS1 in esophageal squamous cell carcinoma Abolfazl Rad 1,2 & Moein Farshchian 3,4 & Mohammad Mahdi Forghanifard 5 & Maryam M. Matin 3 & Ahmad Reza Bahrami 3 & Dirk Geerts 6 & Azadeh A ’rabi 2 & Bahram Memar 7 & Mohammad Reza Abbaszadegan 2,8 Received: 6 May 2015 /Accepted: 7 July 2015 # International Society of Oncology and BioMarkers (ISOBM) 2015 Abstract The three amino acid loop extension (TALE) class myeloid ecotropic viral integration site 1 (MEIS1) homeobox gene is known to play a crucial role in normal and tumor development. In contrast with its well-described cancer stemness properties in hematopoietic cancers, little is known about its role in solid tumors like esophageal squamous cell carcinoma (ESCC). Here, we analyzed MEIS1 expression and its clinical relevance in ESCC patients and also investigated its correlation with the SOX2 self-renewal master transcription factor in the ESCC samples and in the KYSE-30 ESCC cell line. MEIS1 mRNA and protein expression were significantly decreased in ESCC disease (P <0.05). The inverse correlation between MEIS1 mRNA expression and tumor cell metastasis to the lymph nodes (P =0.004) was significant. Also, MEIS1 protein levels inversely correlated to lymph node involvement (P =0.048) and high tumor stage (stages III/IV, P =0.030). The low levels of DNA methylation in the MEIS1 promoter showed that this suppression does not depend on methylation. We showed that downregulation of EZH2 restored MEIS1 ex- pression significantly. Also, we investigated that MEIS1 down- regulation is concomitant with increased SOX2 expression. To the best of our knowledge, this is the first report on the MEIS1 gene in ESCC. The inverse correlation of MEIS1 with metastasis, tumor staging, and the role of EZH2 in methylation, together with its correlation with stemness factor SOX2 expression, led us to predict cancer stemness properties for MEIS1 in ESCC. Keywords ESCC . Downregulation . MEIS1 . SOX2 Abbreviations EC Esophageal carcinoma ESCC Esophageal squamous cell carcinoma ESC Embryonic stem cells CSC Cancer stem cell MEIS1 Myeloid ecotropic viral integration site 1 Abolfazl Rad and Moein Farshchian contributed equally to this work. Electronic supplementary material The online version of this article (doi:10.1007/s13277-015-3780-9) contains supplementary material, which is available to authorized users. * Mohammad Reza Abbaszadegan abbaszadeganmr@mums.ac.ir 1 Department of Biochemistry and Nutrition, Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran 2 Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran 3 Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran 4 Molecular Medicine Research Department, ACECR-Khorasan Razavi branch, Mashhad, Iran 5 Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran 6 Department of Pediatric Oncology/Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands 7 Department of Pathology, Omid Hospital, Mashhad University of Medical Sciences, Mashhad, Iran 8 Medical Genetics Research Center, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran Tumor Biol. DOI 10.1007/s13277-015-3780-9