Aberrant promoter methylation of Runx3 and CHFR genes may be involved in the carcinogenesis and development of GC and may provide useful clues for the prediction of the malignant behaviors of GC.
A significant association was observed between RUNX3 promoter methylation and gastric cancer, with an aggregated odds ratio (OR) of 5.63 (95%CI 3.15, 10.07).
In addition to epigenetic changes in the RUNX3 proximal promoter, genetic changes in the distal promoter may be associated with susceptibility to intestinal-type gastric cancer by increasing promoter activity.
Runt-related transcription factor 3 (RUNX3) is reported as a tumor suppressor gene for gastric cancer, and may be important in the development of hepatocellular carcinoma (HCC).
MR ranged from 0.1% to 69.1% (mean, 18.3%) for LOX, 0.5-74.1% (mean, 15.7%) for p16, 0.2-76.5% (mean, 22.7%) for RUNX3, and 0.6-41.2% (mean, 5.8%) for TIG1 in primary gastric cancers, and from 0.1% to 25.8% (mean, 8.7%) for LOX, 1.0- 23.2% (mean, 10.3%) for p16, 0.7-25.1% (mean, 5.5%) for RUNX3, and 1.8-27.6% (mean, 11.4%) for TIG1 in corresponding non-neoplastic gastric epithelia.
We found no statistically significant associations between RUNX3rs6672420 polymorphism and risk of gastric atrophy, nor between these two RUNX3 polymorphisms and the risk of gastric cancer relative to the subjects with gastric atrophy.
Overall, 55% of GC demonstrated methylation of the RUNX3 promoter; 82% of GC was classified as stable microsatellite instability, 5% as low-level microsatellite instability and 13% as high-level microsatellite instability (MSI-H); mtMSI was detected in 11% of GC.
Our clinical and experimental data provide a novel molecular mechanism for the antitumor activity of RUNX3 and may help design effective therapy targeting RUNX3 pathway to control gastric cancer growth and metastasis.
Although RUNX1 is similar to RUNX3 in both the expression pattern in the stomach and its cell growth-inhibition activity, RUNX1 is not involved in most cases of gastric cancers.
Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray.
Here we discuss recent breakthroughs in our understanding of the mechanisms of RUNX3 in gastric malignancy and comment on possible future trends and perspectives.
Blocking Runx3 expression in immortalized stomach mucosal cells (GES-1) or gastric cancer cells (SGC7901) by Runx3-specific small interfering RNA conferred the cells resistance to chemotherapeutic drugs.