Recent data involve RUNX3 as an important tumor suppressor in gastric cancers and pose interesting questions about how perturbed levels and interspecific competition among RUNX family members may contribute to tumorigenesis.
Among samples obtained from patients with stomach cancer, methylation was observed in both the neoplastic and the corresponding non-neoplastic gastric epithelia; 43% (40/93) and 73% (68/93) for DAP-kinase, and 45% (42/93) and 8% (7/93) for RUNX3, respectively.
The tumorigenicity of human gastric cancer cell lines in nude mice decreased as the level of RUNX3 expression increased, which indicates that RUNX3 is a bona fide tumor suppressor of gastric cancers.
However, there are limited data on the methylation status of RUNX3 in the neoplastic and non-neoplastic tissues in various types of human cancers, including gastric cancer.
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.
These results indicate that silencing of RUNX3 affects expression of important genes involved in aspects of metastasis including cell adhesion, proliferation, apoptosis, and promoting the peritoneal metastasis of gastric cancer.
These findings suggest that RUNX1 and CBFBeta in addition to RUNX3 play some roles in gastric cancers and that roles of RUNX gene family in gastric cancer are more widespread and complex than previously realized.
In addition to the deregulation of mechanisms controlling gene expression, there would also seem to be at least one other mechanism controlling nuclear translocation of RUNX3 that is impaired frequently in gastric cancer.
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.
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.
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.