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.
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.
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.
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.
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.
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.
These results provide further evidence that RUNX3 can function as a tumor suppressor and suggest that practical methods to augment RUNX3 function could be useful in treating of some types of gastric cancer.
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.
The frequencies of high-level methylation in GC tissues for the seven genes were: 48% for APC, 57.33% for WIF-1, 56% for RUNX-3, 50.67% for DLC-1, 52% for SFRP-1, 54.67% for DKK, and 48% for E-cad.
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.
A great number of genes with promoter methylation have been observed in gastric cancer (GC), among which p16INK4A (p16), Mut L homologue 1 (MLH1), Epithelial-cadherin (E-cadherin), Runt-related transcription factor 3 (RUNX3), adenomatous polyposis coli (APC), O(6)-methylguanine-DNA methyltransferase (MGMT), Ras association domain family 1A (RASSF1A) and Death-associated protein kinase (DAPK) have been extensively studied.
RUNX3 showed protein silencing in cancer and normal mucosa, compared to inflammatory peritumoural infiltrate in almost all cases, showing a non-lymphocytic predominant pattern and being correlated with epigenetic silencing.Our results show aberrant promoter's methylation in APC, CDH1, CDKN2A, MLH1 and RUNX3 associated with GC, as well as a non-lymphocytic predominant infiltrate with high expression of RUNX3.
In addition to gene mutation and promoter hypermethylation, cytoplasmic mislocalization has emerged as another major manifestation of RUNX3 dysfunction in malignancies including breast, colorectal and gastric cancers.
Furthermore, the expression of miR‑130a in plasma in gastric cancer patients was upregulated and diagnostic value for gastric cancer of miR-130a is more effective than the tumor markers carcinoembryonic antigen (CEA) and CA-199. miR-130a directly targeted runt‑related transcription factor 3 (RUNX3) and promoted gastric cancer tumorigenesis by targeting RUNX3. miR-130a may therefore be a useful marker for the diagnosis and prognosis of gastric cancer.