Elevated expression of RUNX3 co-expressing with EZH2 in esophageal cancer patients from India

Asad Ur Rehman,Snigdha Saikia,Wasif Mohammad Ali,Real Sumayya Abdul Sattar,Syed Akhtar Husain,Mohammad Askandar Iqbal,Subhash Medhi,Mohammad Kashif,Sundeep Singh Saluja

doi:10.1186/s12935-020-01534-y

Abstract

BackgroundRunt related transcription factor3 (RUNX3) is considered as a tumor suppressor gene (TSG) that functions through the TGF-β dependent apoptosis. Promoter methylation of the CpG islands of RUNX3 and overexpression of enhancer of zeste homolog 2 (EZH2) has been suggested to downregulate RUNX3 in cancer.MethodsHere, we studied the expression of RUNX3 and EZH2 in 58 esophageal tumors along with paired adjacent normal tissue. mRNA levels, protein expressions and cellular localizations of EZH2 and RUNX3 were analyzed using real-time PCR and immunohistochemistry, respectively. DNA methylation was further assessed by the methylation specific-PCR.ResultsCompared to normal tissue, a significant increase in expression of RUNX3 mRNA in 31/57 patient’s tumor tissue (p < 0.04) was observed. The expression of EZH2 was found to be upregulated compared to normal, and a significant positive correlation between EZH2 and RUNX3 expression was observed (p = 0.002). 22 of the 27 unmethylated cases at the promoter region of the RUNX3 had elevated RUNX3 protein expression (p < 0.001).ConclusionThe data presented in this study provide new insights into the biology of RUNX3 and highlights the need to revisit our current understanding of the role of RUNX3 in cancer.

Highlights

Runt related transcription factor3 (RUNX3) is considered as a tumor suppressor gene (TSG) that functions through the TGF-β dependent apoptosis
*Correspondence: sundeepsaluja@yahoo.co.in; akhtarhusain2000@yahoo. com; shusain@jmi.ac.in 1 Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India 6 Department of Gastrointestinal Surgery, G B Pant Hospital & Maulana Azad Medical College, New Delhi, India Full list of author information is available at the end of the article (CaEs), a cancer of the gastrointestinal tract has, become eighth most common cancer worldwide and, leads at sixth position in context of the deaths due to cancers [2]. 450,000 people worldwide are currently suffering from CaEs which exists majorly as esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) [3, 4]
No Absence of promoter DNA methylation correlated with upregulated RUNX3 In our study, we found unmethylated CpG in RUNX3 in 47.36% (27/57) samples and out of these 27 samples 81.48% (22/27) samples showed elevated expression of the RUNX3 protein in the tumor as compared to the normal tissue (Fig. 2)

Summary

Introduction

Runt related transcription factor (RUNX3) is considered as a tumor suppressor gene (TSG) that functions through the TGF-β dependent apoptosis. Thousands of people every year dwell with one of the hundred types of cancer and it has been estimated that around 8.2 million people die due to cancer [1]. Esophageal cancer (CaEs), a cancer of the gastrointestinal tract has, become eighth most common cancer worldwide and, leads at sixth position in context of the deaths due to cancers [2]. 450,000 people worldwide are currently suffering from CaEs which exists majorly as esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) [3, 4]. Adenocarcinoma occurs mainly in Western countries and often preceded with the GERD whereas ESCC found to be the predominant type of CaEs in Asia pacific region [5]. Surgery is the most opted therapy for esophageal tumor [6].

Methods

Discussion

Conclusion