Our data from bioinformatic and luciferase reporter gene assays identified that miR-5195-3p targeted the mRNA 3'-UTR of Krüppel-like factor 5 (KLF5), which is a proven proto-oncogene in bladder cancer. miR-5195-3p sharply reduced KLF5 expression and suppressed the expression or activation of its several downstream genes that are kinases improving cell survival or promoting cell cycle regulators, including ERK1/2, VEGFA, and cyclin D1.
In addition, phosphorylated ERK1/2 and p38, key members of mitogen-activated protein kinase (MAPK) family regulating BCa tumorigenesis, were strongly decreased.
We show that Notch activation in bladder cancer cells suppresses proliferation both in vitro and in vivo by directly upregulating dual-specificity phosphatases (DUSPs), thus reducing the phosphorylation of ERK1 and ERK2 (ERK1/2).
Pancreatic secretory trypsin inhibitor causes autocrine-mediated migration and invasion in bladder cancer and phosphorylates the EGF receptor, Akt2 and Akt3, and ERK1 and ERK2.
The transient transfection of bladder cancer cells with ERK1/2 knock down (si-ERK1/2) and dominant negative p38 (DNp38) suppressed IL-28A-induced migration.
In the current study, we investigated the role of two different MAPKs (ERK1/2 and p38) by using their specific inhibitors PD98059 and SB203580 respectively, on bladder cancer growth in two cell lines derived from different tumor stages.
Activation of extracellular regulated kinases (ERK1/2) predicts poor prognosis in urothelial bladder carcinoma and is not associated with B-Raf gene mutations.