Tumor Biology

, Volume 37, Issue 2, pp 1715–1725 | Cite as

Predicting the molecular role of MEIS1 in esophageal squamous cell carcinoma

  • Abolfazl Rad
  • Moein Farshchian
  • Mohammad Mahdi Forghanifard
  • Maryam M. Matin
  • Ahmad Reza Bahrami
  • Dirk Geerts
  • Azadeh A’rabi
  • Bahram Memar
  • Mohammad Reza Abbaszadegan
Original Article


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.


ESCC Downregulation MEIS1 SOX2 



Esophageal carcinoma


Esophageal squamous cell carcinoma


Embryonic stem cells


Cancer stem cell


Myeloid ecotropic viral integration site 1


Myeloid/lymphoid or mixed lineage leukemia


Methylation-specific PCR


Leukemia stem cell


Pre-B cell leukemia homeobox


Three amino acid loop extension



The authors gratefully acknowledge the scientific and technical support of colleagues at the Division of Human Genetic, Avicenna Research Institute (Mashhad University) and the Department of Biology, Ferdowsi University of Mashhad. In addition, we thank Dr. Heydar Parsaee (Department of Pharmacology, Mashhad University) and Dr. Thomas Mikeska (Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne, Australia) for their technical assistances. This study was a MSc thesis and supported by a grant from Mashhad University of Medical Sciences (# 89751).

Conflict of interest


Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved beforehand by the local Ethics Committee. Informed, declared consent was obtained from all individual participants included in the study, and is on record. This article does not contain any studies with animals performed by any of the authors.

Supplementary material

13277_2015_3780_MOESM1_ESM.tif (329 kb)
Supplemental Figure 1 SOX2 mRNA detection in 50 ESCC and matched adjacent non-tumoral tissue samples. SOX2 mRNA expression is higher in tumor than in adjacent non-tumoral tissue, but this difference does not reach significance. SOX2 mRNA expression was determined with qRT-PCR, with GAPDH as the reference gene. Shown are the 2log median centered mean values, the error bars represent the SD. A two-sided t-test was used to assess the statistical difference between ESCC and adjacent non-tumoral tissue. (TIFF 329 kb)
13277_2015_3780_Fig7_ESM.gif (30 kb)

High resolution image (GIF 30 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • 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
  1. 1.Department of Biochemistry and Nutrition, Cellular and Molecular Research CenterSabzevar University of Medical SciencesSabzevarIran
  2. 2.Division of Human Genetics, Immunology Research Center, Avicenna Research InstituteMashhad University of Medical SciencesMashhadIran
  3. 3.Department of Biology, Faculty of ScienceFerdowsi University of MashhadMashhadIran
  4. 4.Molecular Medicine Research DepartmentACECR-Khorasan Razavi branchMashhadIran
  5. 5.Department of Biology, Damghan BranchIslamic Azad UniversityDamghanIran
  6. 6.Department of Pediatric Oncology/HematologyErasmus University Medical CenterRotterdamThe Netherlands
  7. 7.Department of Pathology, Omid HospitalMashhad University of Medical SciencesMashhadIran
  8. 8.Medical Genetics Research Center, Medical SchoolMashhad University of Medical SciencesMashhadIran

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