title: Predicting the molecular role of MEIS1 in esophageal squamous cell carcinoma.
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 expression significantly. Also, we investigated that MEIS1 downregulation 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.
authors: Department of Biochemistry and Nutrition, Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran.|Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
authors: Abolfazl
authors: A
authors: Rad
authors: Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.|Molecular Medicine Research Department, ACECR-Khorasan Razavi branch, Mashhad, Iran.
authors: Moein
authors: M
authors: Farshchian
authors: Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran.
authors: Mohammad Mahdi
authors: MM
authors: Forghanifard
authors: Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
authors: Maryam M
authors: MM
authors: Matin
authors: Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
authors: Ahmad Reza
authors: AR
authors: Bahrami
authors: Department of Pediatric Oncology/Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Dirk
authors: D
authors: Geerts
authors: Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
authors: Azadeh
authors: A
authors: A'rabi
authors: Department of Pathology, Omid Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
authors: Bahram
authors: B
authors: Memar
authors: Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran. abbaszadeganmr@mums.ac.ir.|Medical Genetics Research Center, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran. abbaszadeganmr@mums.ac.ir.
authors: Mohammad Reza
authors: MR
authors: Abbaszadegan
mesh_terms: D000368:Aged; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors
keywords: Downregulation; ESCC; MEIS1; SOX2