Meysam Moghbeli1, Abolfazl Rad2, Moein Farshchian3, Negin Taghehchian1, Mehran Gholamin1, Mohammad Reza Abbaszadegan4,5. 1. Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran. 2. Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran. 3. Molecular Medicine Research Department, ACECR-Khorasan Razavi Branch, Mashhad, Iran. 4. Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran. abbaszadeganmr@mums.ac.ir. 5. Medical Genetics Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. abbaszadeganmr@mums.ac.ir.
Abstract
PURPOSE: Homeobox (HOX) transcription factors are critical regulators of cell fate, stem cell functions, and gastrointestinal development. They require three-amino acid loop extension (TALE) homeodomain proteins such as Meis1 to enhance their transcriptional efficiencies. There are complicated associations between different signaling pathways such as the Wnt and NOTCH and tumor progression. It has been investigated that GSK-3 as an important component of the Wnt pathway facilitates the expression of HOX target genes. Therefore, in the present study, we assessed the probable correlation between Wnt, NOTCH, and HOX genes in esophageal squamous cell carcinoma (ESCC) progression and metastasis through the correlational study between the Msi1 as an important activator for both of the NOTCH and Wnt pathways and Meis1. METHODS: Levels of Meis1 and Msi1 messenger RNA (mRNA) expression in 51 ESCC patients were compared to the normal tissues using real-time polymerase chain reaction. RESULTS: Only 3 out of 51 (5.9 %) cases had Meis1/Msi1 overexpression and also 3/51 (5.9 %) cases had Meis1/Msi1 underexpression. There was a significant correlation between the Msi1 and Mesi1 mRNA expression (p = 0.037). All of the Msi1/Meis1 underexpressed tumors were poorly differentiated (p = 0.003). Meis1 under/Msi1 overexpressed cases also were in T3 tumor depth of invasion (p = 0.019). And there was a significant correlation between the Msi1/Meis1 underexpression and gender (p = 0.045). CONCLUSIONS: Our results show that Meis1 may have a positive feedback with Msi1 during the ESCC progression.
PURPOSE: Homeobox (HOX) transcription factors are critical regulators of cell fate, stem cell functions, and gastrointestinal development. They require three-amino acid loop extension (TALE) homeodomain proteins such as Meis1 to enhance their transcriptional efficiencies. There are complicated associations between different signaling pathways such as the Wnt and NOTCH and tumor progression. It has been investigated that GSK-3 as an important component of the Wnt pathway facilitates the expression of HOX target genes. Therefore, in the present study, we assessed the probable correlation between Wnt, NOTCH, and HOX genes in esophageal squamous cell carcinoma (ESCC) progression and metastasis through the correlational study between the Msi1 as an important activator for both of the NOTCH and Wnt pathways and Meis1. METHODS: Levels of Meis1 and Msi1 messenger RNA (mRNA) expression in 51 ESCC patients were compared to the normal tissues using real-time polymerase chain reaction. RESULTS: Only 3 out of 51 (5.9 %) cases had Meis1/Msi1 overexpression and also 3/51 (5.9 %) cases had Meis1/Msi1 underexpression. There was a significant correlation between the Msi1 and Mesi1 mRNA expression (p = 0.037). All of the Msi1/Meis1 underexpressed tumors were poorly differentiated (p = 0.003). Meis1 under/Msi1 overexpressed cases also were in T3 tumor depth of invasion (p = 0.019). And there was a significant correlation between the Msi1/Meis1 underexpression and gender (p = 0.045). CONCLUSIONS: Our results show that Meis1 may have a positive feedback with Msi1 during the ESCC progression.
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