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

Research output: Contribution to JournalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)1715-25
Number of pages11
JournalTumor Biology
Volume37
Issue number2
DOIs
Publication statusPublished - Feb 2016

Keywords

  • Aged
  • Blotting, Western
  • Carcinoma, Squamous Cell/genetics
  • Esophageal Neoplasms/genetics
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins/genetics
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins/genetics
  • Real-Time Polymerase Chain Reaction
  • SOXB1 Transcription Factors/genetics
  • Transcriptome

Cite this