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

Abstract

Background Runt 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. Methods Here, 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. Results Compared 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). Conclusion The 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.

RUNX3 promoter methylation is associated with oral squamous cell carcinoma location

“…First, we observed the occurrence of a fairly high frequency of promoter methylation of RUNX3 in OSCC. Similar observations of elevated methylation of this gene had been made in colorectal cancer (SHIN et al, 2018); lung cancer (ZHAO et al, 2019); gastric cancer (LIN et al, 2017); bladder cancer (LEE and SONG, 2017); hepatocellular cancer (GAOFENG et al, 2017); esophageal cancer (REHMAN et al, 2020) and OSCC in a Brazillian study (CORDEIRO-SILVA et al, 2012).…”

Identification of four genes and biological characteristics of esophageal squamous cell carcinoma by integrated bioinformatics analysis

“…ESCC is a malignant tumor that poses a serious threat to human health due to its high incidence rate and low 5-year survival rate. Although numerous studies have investigated the mechanisms underlying ESCC, effective biomarkers for the diagnosis, prognosis and therapeutic targeting of ESCC remain scarce, and the mechanisms governing ESCC have not been fully elucidated [ 27 , 28 ]. In the present study, six high-quality GEO datasets were selected to identify the hub genes associated with ESCC, as well as their associated biological pathways by integrated bioinformatic analysis.…”

Long non-coding RNA LINC01215 promotes epithelial-mesenchymal transition and lymph node metastasis in epithelial ovarian cancer through RUNX3 promoter methylation

“…A higher RUNX3 gene promoter hyper-methylation rate is found in GC tumor tissues compared with that in the normal tissues [15] . Promotion of the methylation of the CpG islands in the promoter region of RUNX3 has been suggested to downregulate the expression of RUNX3 [16] . Moreover, the repression of RUNX3 modulated by hyper-methylation is closely linked to unsatisfactory clinical outcomes in Type II EOC [17] .…”