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.
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).
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.
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.
Therefore, our findings provide novel evidence that STAT3 may be a potential therapeutic target for GC treatment and pSTAT3(Tyr705) expression can predict prognosis in GC.
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.
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.
Therapeutic intervention of STAT3 in reversing the epigenetic status of GATA6 could benefit the treatment of gastric cancer and is worthy of further investigation.
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.
The results indicate that the interaction between STAT3 and Skp2/p27/p21 pathway plays an important role in mediating the motility, migration and invasion of gastric cancer cells, and inhibition of STAT3 may be a useful therapeutic approach for metastasis of gastric cancer, but caution needs to be taken for its effects on Skp2/p27/p21 pathway.
The present study demonstrated that miR-1224 is downregulated in intestinal-type GC. miR-1224 inhibits the metastasis of intestinal-type GC by suppressing FAK-mediated activation of the STAT3 and NF-κB pathways, and subsequent EMT. miR-1224 could represent an important prognostic factor in intestinal-type GC.
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).
The expressions of HER-2 and STAT3 in GC tissues were increased, but SOCS3 expression showed an evident decrease with the change of depth of invasion, lymph node metastasis (LNM), and tumor node metastasis staging (all P < 0.05).
The downregulation of GSDMD accelerated S/G<sub>2</sub> cell transition by activating extracellular signal regulated kinase, signal transducer and activator of transcription 3 and phosphatidylinositol 3 kinase/protein kinase B signaling pathways and regulating cell cycle-related proteins in GC.
Taken together, we reveal that miR-93-5p overexpression is associated with the poor survival of GC patients and miR-93-5p-IFNAR1 axis promotes GC metastasis through activation of STAT3 pathway.
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.