Keratin 17 knockdown suppressed malignancy and cisplatin tolerance of bladder cancer cells, as well as the activation of AKT and ERK pathway
Abstract
Introduction. Bladder cancer (BCa) is one the most common urinary system malignancies and approximately one quarter of diagnosis is invasive muscle-invasive BCa. Accumulating evidence revealed that keratin 17 (KRT17) is closely related to the prognosis and progression of various tumors including a recent study also implying the potential role of KRT17 in the diagnosis of BCa. However, the specific role of KRT17 in BCa remains to be elucidated.
Material and methods. The expression of KRT17 in 5637 BCa cells and SV-HUC-1 normal human urothelial cells was detected using quantitative real-time PCR (qRT-PCR) and western blot. Short hairpin RNA targeting KRT17 was used to knockdown KRT17 in BCa cells. The colony formation was assessed and the proliferation of cells was studied by Cell Counting Kit-8 (CCK-8). Invasion and epithelial-mesenchymal transition (EMT) capacity of BCa cells were assessed using transwell assay and western blot, respectively. Cisplatin sensitivity of cancer cells was measured by evaluating the cell viability using CCK-8 assay. The downstream pathway of KRT17 was explored by western blot.
Results. The expression of KRT17 was elevated in BCa cells in comparison with the normal human urothelial cell at the mRNA and protein levels. The in vitro assays demonstrated that KRT17 interference affected the proliferation, colony formation and invasion capacity of BCa cells, as well as EMT. Furthermore, knockdown
of KRT17 enhanced cisplatin sensitivity in BCa cells. Mechanically, KRT17 ablation led to the inactivation of both AKT and ERK pathways.
Conclusions. Our results elucidate the vital role of KRT17 in the development of malignancy of BCa cells, probably by the activation of AKT and ERK pathways and suggest that it may represent a novel therapeutic target for BCa.
Keywords: bladder cancerSV-HUC-1 cells5637 cellskeratin 17shRNAEMTproliferationinvasioncisplatin sensitivityAKTERK
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