We also found that a significant decreased GCa risk was associated with STAT3 rs1053004G variant genotypes (adjusted OR = 0.84; 95% CI = 0.71-0.99 for AG + GG vs. AA).
Our study provides evidence that STAT3rs744166 G allele and infection with CagA-positive H. pylori with higher number of EPIYA-C segments are independent risk factors for gastric cancer.
There is a strong link between pri-miR-124-1 rs531564 and STAT3rs1053023 and gastric cancer that may be pathogenic, and so worthy of further investigation.
These findings indicated that miR-125a may control the HAS1 expression in GC progression by targeting STAT3, which is likely to facilitate a better understanding of the regulation mechanisms of miR-125a in GC.
Conversely, knockdown of GRIM-19 induced aberrant STAT3 activation and accelerated GC cell growth in vitro and in vivo, and this could be partly attenuated by the blockage of STAT3 activation.
These data suggest that SOCS3 is an antigastric tumor gene that suppresses leptin overexpression and ObRb/STAT3 hyperactivation, supporting the hypothesis that the leptin/ObRb/STAT3 axis accelerates tumorigenesis and that it may represent a new therapeutic target for the treatment of gastric cancer.
The results indicated that high mRNA expression of all individual STATs, except STAT3 and STAT6, were significantly associated with favorable overall survival (OS) in GC.
With multivariate logistical regression analysis, SOCS-3, STAT-3, and the status of extragastric nodal metastasis were identified to be the independent factors of the lymph node metastasis from GC.
Dysregulated Stat3 activation may play an important role in VEGF overexpression and elevated angiogenic phenotype in gastric cancer and contribute to gastric cancer development and progression.
Taken together, these findings indicate that down-regulation of miR-874 contributes to tumor angiogenesis through STAT3 in GC, highlighting the potential of miR-874 as a target for human GC therapy.
Therefore, miR-31 could be a useful biomarker for monitoring GC development and progression, and also could have a therapeutic potential by targeting SGPP2, Smad4 and STAT3 for GC therapy.