Abstract
This study aims to investigate the biological role of RhoB in clear cell renal cell carcinoma (ccRCC). The expression of RhoB was examined in specimens of patients and cell lines by Western blot and Immunohistochemistry. The correlation between RhoB expression and clinicopathologic variables was also analyzed. The effects of RhoB on cell proliferation, cell cycle, cell apoptosis, and invasion/migration were detected by over-expression and knockdown of RhoB level in ccRCC cells via plasmids and RNAi. The results showed that RhoB was low-expressed in ccRCC surgical specimens and cell lines compared with adjacent normal renal tissues and normal human renal proximal tubular epithelial cell lines (HKC), and its protein expression level was significantly associated with the tumor pathologic parameter embracing tumor size(P = 0.0157), pT stage(P = 0.0035), TNM stage(P = 0.0024) and Fuhrman tumor grade(P = 0.0008). Further, over-expression of RhoB remarkably inhibited the cancer cell proliferation, colony formation and promoted cancer cell apoptosis, and aslo reduced the invasion and migration ability of ccRCC cells. Interestingly, up-regulation of RhoB could induce cell cycle arrest in G2/M phase and led to cell cycle regulators(CyclineB1,CDK1) and pro-apoptotic protein(casp3,casp9) aberrant expression. Moreover, knockdown of RhoB in HKC cells promoted cell proliferation and migration. Taken together, our study indicates that RhoB expression is decreased in ccRCC carcinogenesis and progression. Up-regulation of RhoB significantly inhibits ccRCC cell malignant phenotype. These findings show that RhoB may play a tumor suppressive role in ccRCC cells, raising its potential value in futural therapeutic target for the patients of ccRCC.
Highlights
Clear cell renal cell carcinoma originates from proximal tubule cells, and is one of the most common histological subtypes of renal cell carcinomas. ccRCC is the second leading cause of death among all types of urologic cancers[1, 2]
CcRCC is resistant to conventional cytotoxic agents, in addition to surgery[4]. the new targeted therapies have produced dramatic clinical effects for the treatment of metastatic renal-cell carcinoma (RCC), such targeted therapies remain unsatisfactory because some patients are resistant to therapy [5].further studies are necessary to investigate the tumorigenesis and progression of ccRCC and to explore new therapeutic targets to improve the efficiency of ccRCC treatment
RhoB expression is decreased in ccRCC tissues and cell lines
Summary
Clear cell renal cell carcinoma (ccRCC) originates from proximal tubule cells, and is one of the most common histological subtypes of renal cell carcinomas. ccRCC is the second leading cause of death among all types of urologic cancers[1, 2]. CcRCC is the second leading cause of death among all types of urologic cancers[1, 2]. Approximately 25% to 30% of the patients with ccRCC present metastasis at the time of diagnosis, and overall survival is usually very poor in the follow-up period[3]. CcRCC is resistant to conventional cytotoxic agents, in addition to surgery[4]. the new targeted therapies have produced dramatic clinical effects for the treatment of metastatic renal-cell carcinoma (RCC), such targeted therapies remain unsatisfactory because some patients are resistant to therapy [5].further studies are necessary to investigate the tumorigenesis and progression of ccRCC and to explore new therapeutic targets to improve the efficiency of ccRCC treatment. RhoB is a member of the Rho family of small GTPases, which regulates actin stress fibers, cytoskeletal actin organization and vesicle transport, in cancer cells, RhoB modulates proliferation, survival, invasion and angiogenic capacity[6]. Overexpression of RhoB in human tumor cells results in inhibition of signal transduction pathways involved in oncogenesis and tumor survival, as well as apoptosis[13]
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