title: Overexpression of Numb suppresses growth, migration, and invasion of human clear cell renal cell carcinoma cells.
abstract: The objective of the study was to investigate the impact of Numb on cell growth, cell migration, and invasion in human clear cell renal cell carcinoma (ccRCC). Endogenous expression of Numb was evaluated in the ccRCC cell lines (786-O, Caki-1, and Caki-2) and control reference human renal proximal tubular epithelial cells. Numb expression was decreased in the ccRCC cells compared with the control cells (P < 0.01). Then, 786-O and Caki-1 cells described as suitable transfection hosts were used in transfection to carry out biological function studies. The three experimental groups were as follows: Numb-ORF (transfected with Numb-ORF plasmid), blank-vector (transfected with pCMV6-entry), and cell-alone group (no DNA). Numb expression in the Numb-ORF groups was significantly higher than that in the controls (P < 0.01). Cell growth was remarkably reduced (P < 0.01), and the number of migrating or invading cells was reduced (P < 0.01) in the Numb-ORF groups compared with controls. Furthermore, the ratio of G0/G1 phase in the Numb-ORF group of 786-O cells was increased, and the S phase fraction and proliferation index was decreased (P < 0.01). Cyclin D1 and MMP-9 expression was reduced in the Numb-ORF groups compared with controls. Here, we have provided data for attenuated Numb expression in the ccRCC cells. Overexpression of Numb could induce G0/G1 phase arrest and inhibit cell proliferation, migration, and invasion. The suppressive effects might be due to downregulation of cyclin D1 or MMP-9 expression. Taken together, our data suggest that Numb may possibly function as a tumor suppressor involved in the carcinogenesis of ccRCC.
authors.affiliation: Department of Urology, Aerospace Central Hospital, No. 15 Yuquan Road, Beijing, 100049, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Sima
authors.forename: Bao
authors.initials: B
authors.lastname: Zhang
authors.forename: Yuanzi
authors.initials: Y
authors.lastname: Yu
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Sima
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Mao
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D019938:Cyclin D1 / Q000096:biosynthesis; D016193:G1 Phase / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C113026:NUMB protein, human; D019938:Cyclin D1; D020780:Matrix Metalloproteinase 9