The positive rate of unphosphorylated STAT3 expression was dramatically higher in GC tissues (86.7%) compared to that in adjacent normal tissues (16.7%) and SG tissues (10.0%) (P<0.05).
Furthermore, we found that there were significant associations between STAT3 expression, pSTAT3 expression, EGFR expression, and lymph node metastasis in GC tissues.
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.
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).
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.
Activation of the signal transducer and activator of transcription 3 (STAT3) is observed in multiple cancer types, including gastric cancer, and represents a potential drug target for chemotherapy.
STAT3 signaling was correlated with EZH2 expression in GC (R = 0.373, P = 0.003), which was consistent with our data showing that STAT3 as the transcriptional factor enhanced EZH2 transcriptional activity by binding the relative promoter region (-214 ~ -206).
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.
Taken together, our results indicate that CD24 mediates gastric carcinogenesis and may promote GC progression by suppressing apoptosis and promoting invasion, with the activation of STAT3 playing a critical role.