Overexpression of β-arrestin2 induces G1-phase cell cycle arrest and suppresses tumorigenicity in renal cell carcinoma.

Abstract The objective of this study was to investigate the role of β-arrestin2 in the proliferation, migration, apoptosis, cell cycle and clone formation of renal cell carcinoma (RCC) cell lines and to explore the possible mechanism of β-arrestin2 in RCC invasion and metastasis to find a new therapeutic target. Cell proliferation, migration, apoptosis, cell cycle and clone formation were analyzed after RCC cell lines (786-0 and CaKi) and transfected with β-arrestin2 overexpression plasmid. Using small interfering RNA (siRNA) interference technology abrogates β-arrestin2 overexpression, and changes in cell proliferation, migration, apoptosis, cell cycle and clone formation were analyzed. The expression levels of total IkBa, IkBa phosphorylation (P-IkBa) and NFkB P65 in 786-0 cells were examined after transfection with β-arrestin2 overexpression plasmid to explore the mechanism of β-arrestin2. After transfection with β-arrestin2 overexpression plasmid, the abilities of proliferation, migration, and cloning formation in 786-0 and CaKi cells decreased significantly, the apoptosis rate increased significantly, and the cell cycles were blocked in the G1 phase. After siRNA reduced the expression of β-arrestin2, the abilities to proceed through cell proliferation, migration, apoptosis, the cell cycle and clone formation were enhanced. The P-IkBa level in 786-0 cells decreased significantly after transfection, while the expression of P-IkBa in the control group remained high. The expression of NFkB P65 was high in the control group and low in the transfection group. The overexpression of β-arrestin2 can inhibit the growth of RCC cells in vitro, and β-arrestin2 acts as a tumor suppressor gene in RCC. The main mechanism may directly suppress the phosphorylation of IkBa and indirectly suppress NFkB activation. Thus, β-arrestin2 is expected to be an important marker of RCC prognosis and a new therapeutic target.