The identification of the miR-146b/AUF1/ETS2/MMP2 mechanism for promoting bladder cancer invasion provides significant insights into understanding the nature of bladder cancer metastasis.
These findings, together with our previous results showing X-link inhibitor of apoptosis protein mediating mRNA stabilization of both RhoGDIβ and mmp-2, reveal the nature of the MMP-2 regulatory network, which leads to MMP-2 overexpression and BC invasion.
Herein, we report the novel concept that miR-20b exerts a suppressive effect on both cell cycle-modulated proliferation and MMP-2-mediated migration and invasion in bladder cancer EJ cells.
For the MMP2-1306 C/T polymorphism, there was a negative association with the T allele for bladder cancer in the Asian population (TT+TC vs. CC: OR = 0.41, 95% CI = 0.18-0.94, pheterogeneity = 0.195).
Knockdown of GATA3 in the bladder cancer lines (5637, TCC-SUP, J82) resulted in promotion of cell migration and invasion as well as increases in the expression of their related molecules, such as vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, and MMP-9, and the activity of MMP-2 and MMP-9.
The combined genotype MMP2-1306C/T (rs243865) allele T with MMP9 -1562C/T (rs3918242) allele T was found to increase BC risk (OR 2.00, 95% CI 1.10-3.62; P = 0.022).
MMP-9, MMP-2 and its specific inhibitors expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue collected from 40 patients with BC submitted to transurethral resection of bladder.
The levels of circulating proMMP-2, active MMP-2, proMMP-9, TIMP-1, TIMP-2 and MMP-2:TIMP-2 complex of 84 patients with bladder cancer were measured by ELISA.
The results indicate that TIMP-2 and MMP-2:TIMP-2 complex associate with favorable clinical course and could be used as a novel prognostic indicators in bladder cancer.