Overexpression of β-arrestin2 induces G1-phase cell cycle arrest and suppresses tumorigenicity in renal cell carcinoma. 2017

Y-J Cao, and Y-J Zhou, and X-Z He, and C-X Zhou, and L Cui, and Q-F Zhuang, and R-F Xu
Department of Urology, the Third Affiliated Hospital of Soochow University, Changzhou, China. czyyxrf@163.com.

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.

UI MeSH Term Description Entries
D007680 Kidney Neoplasms Tumors or cancers of the KIDNEY. Cancer of Kidney,Kidney Cancer,Renal Cancer,Cancer of the Kidney,Neoplasms, Kidney,Renal Neoplasms,Cancer, Kidney,Cancer, Renal,Cancers, Kidney,Cancers, Renal,Kidney Cancers,Kidney Neoplasm,Neoplasm, Kidney,Neoplasm, Renal,Neoplasms, Renal,Renal Cancers,Renal Neoplasm
D002292 Carcinoma, Renal Cell A heterogeneous group of sporadic or hereditary carcinoma derived from cells of the KIDNEYS. There are several subtypes including the clear cells, the papillary, the chromophobe, the collecting duct, the spindle cells (sarcomatoid), or mixed cell-type carcinoma. Adenocarcinoma, Renal Cell,Carcinoma, Hypernephroid,Grawitz Tumor,Hypernephroma,Renal Carcinoma,Adenocarcinoma Of Kidney,Adenocarcinoma, Renal,Chromophil Renal Cell Carcinoma,Chromophobe Renal Cell Carcinoma,Clear Cell Renal Carcinoma,Clear Cell Renal Cell Carcinoma,Collecting Duct Carcinoma,Collecting Duct Carcinoma (Kidney),Collecting Duct Carcinoma of the Kidney,Nephroid Carcinoma,Papillary Renal Cell Carcinoma,Renal Cell Cancer,Renal Cell Carcinoma,Renal Cell Carcinoma, Papillary,Renal Collecting Duct Carcinoma,Sarcomatoid Renal Cell Carcinoma,Adenocarcinoma Of Kidneys,Adenocarcinomas, Renal Cell,Cancer, Renal Cell,Carcinoma, Collecting Duct,Carcinoma, Collecting Duct (Kidney),Carcinoma, Nephroid,Carcinoma, Renal,Carcinomas, Collecting Duct,Carcinomas, Collecting Duct (Kidney),Carcinomas, Renal Cell,Collecting Duct Carcinomas,Collecting Duct Carcinomas (Kidney),Hypernephroid Carcinoma,Hypernephroid Carcinomas,Hypernephromas,Kidney, Adenocarcinoma Of,Nephroid Carcinomas,Renal Adenocarcinoma,Renal Adenocarcinomas,Renal Carcinomas,Renal Cell Adenocarcinoma,Renal Cell Adenocarcinomas,Renal Cell Cancers,Renal Cell Carcinomas,Tumor, Grawitz
D002453 Cell Cycle The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE. Cell Division Cycle,Cell Cycles,Cell Division Cycles,Cycle, Cell,Cycle, Cell Division,Cycles, Cell,Cycles, Cell Division,Division Cycle, Cell,Division Cycles, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071560 beta-Arrestin 2 A beta-arrestin that functions similarly to BETA-ARRESTIN 1 in regulating signaling by G-PROTEIN-COUPLED RECEPTORS. It is expressed at high levels in the central nervous system where it may regulate signaling by SYNAPTIC RECEPTORS. ARRB2 Protein,Arrestin, beta 2,Arrestin-3,Arrestin 3,beta 2 Arrestin,beta Arrestin 2
D014162 Transfection The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES. Transfections
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D059447 Cell Cycle Checkpoints Regulatory signaling systems that control the progression through the CELL CYCLE. They ensure that the cell has completed, in the correct order and without mistakes, all the processes required to replicate the GENOME and CYTOPLASM, and divide them equally between two daughter cells. If cells sense they have not completed these processes or that the environment does not have the nutrients and growth hormones in place to proceed, then the cells are restrained (or "arrested") until the processes are completed and growth conditions are suitable. Cell Cycle Arrest,Cell Cycle Control,Cell Cycle Transition Points,Cell Cycle-Transition Points,Arrest, Cell Cycle,Arrests, Cell Cycle,Cell Cycle Arrests,Cell Cycle Checkpoint,Cell Cycle Controls,Cell Cycle-Transition Point,Checkpoint, Cell Cycle,Checkpoints, Cell Cycle,Control, Cell Cycle,Controls, Cell Cycle,Cycle-Transition Point, Cell,Point, Cell Cycle-Transition

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