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.
Furthermore, the IHC staining for GC tissues showed that expression level of SIRT6 was decreased in GC tissues while the expression level of p-STAT3 was increased in GC tissues.
Current evidence indicates that the oncogenic transcription factor signal transducers and activators of transcription 3 (STAT3) is inappropriately activated in multiple malignancies, including gastric cancer.
Therapeutic intervention of STAT3 in reversing the epigenetic status of GATA6 could benefit the treatment of gastric cancer and is worthy of further investigation.
Subgroup analysis showed that elevated STAT3 expression was associated with poor prognosis of gastric cancer, lung cancer, gliomas, hepatic cancer, osteosarcoma, prostate cancer, pancreatic cancer but better prognosis of breast cancer.
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).
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).
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.
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.
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.
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.
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.