Abstract
Tyrosine kinase receptor macrophage stimulating 1 receptor (MST1R, also known as RON) contributes to the transformation and malignant progression observed in epithelial cells. The purpose of the present study is to assess the value of RON as a potential target in bladder cancer (BC) therapeutics. The expression profile of RON in BC tissues and adjacent noncancerous tissues was detected via immunohistochemistry. The rate of positive RON expression differed significantly between bladder urothelial cancer tissues (54.7%) and paraneoplastic tissues (29.4%) (P<0.05). RON expression was positively associated with the number of tumors per patient, histological grading, pathological stage and distant metastasis (all P<0.05). Downregulation of RON expression using small interfering RNAs inhibited cell growth, cell migration and promoted cell apoptosis in the 5637 cell line. RON inhibition induced cell cycle arrest at the G1/S boundary following an increase of cyclin-dependent kinase inhibitor 1B and cyclin-dependent kinase inhibitor 1A, and a decrease of cyclin D1, cyclin D3 and cyclin-dependent kinase 4 expression. Furthermore, knockdown of RON significantly blocked signal transduction, including downstream protein kinase B and mitogen-activated protein kinase pathways. These results indicated that RON serves a notable role in BC and is a potential target of therapeutic intervention.