MCPIP1 overexpression in human neuroblastoma cell lines causes cell‐cycle arrest by G1/S checkpoint block. Issue 5 (9th January 2020)

• Record Type: Journal Article
• Authors: Boratyn, Elżbieta; Nowak, Iwona; Karnas, Elżbieta; Ryszawy, Damian; Wnuk, Dawid; Polus, Anna; Durbas, Małgorzata; Horwacik, Irena; Rokita, Hanna
• Is Part Of: Journal of cellular biochemistry. Volume 121:Issue 5/6(2020)
• Page Start: 3406
• Page End: 3425
• Publication Date: 2020-01-09
• Subjects: cell cycle -- G1/S cell‐cycle arrest -- MCPIP1 -- neuroblastoma; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.29614
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Monocyte chemoattractant protein‐1‐induced protein 1 (MCPIP1) has a multidomain structure, which assures its pleiotropic activity. The physiological functions of this protein include repression of inflammatory processes and the prevention of immune disorders. The influence of MCPIP1 on the cell cycle of cancer cells has not been sufficiently elucidated. A previous study by our group reported that overexpression of MCPIP1 affects the cell viability, inhibits the activation of the phosphoinositide‐3 kinase/mammalian target of rapamycin signalling pathway, and reduces the stability of the MYCN oncogene in neuroblastoma (NB) cells. Furthermore, a decrease in expression and phosphorylation levels of cyclin‐dependent kinase (CDK) 1, which has a key role in the M phase of the cell cycle, was observed. On the basis of these previous results, the purpose of our present study was to elucidate the influence of MCPIP1 on the cell cycle of NB cells. It was confirmed that ectopic overexpression of MCPIP1 in two human NB cell lines, KELLY and BE(2)‐C, inhibited cell proliferation. Furthermore, flow cytometric analyses and imaging of the cell cycle with a fluorescence ubiquitination cell‐cycle indicator test, demonstrated that overexpression of MCPIP1 causes an accumulation of NB cells in the G1 phase of the cell cycle, while the possibility of an increase in G0 phase due to induction of quiescence or senescence was excluded. Additional assessment of the molecular machinery responsible for the transition between the cell‐cycle phases confirmed that MCPIP1 overexpression reduced the expression of cyclins A2, B1, D1, D3, E1, and E2 and decreased the phosphorylation of CDK2 and CDK4, as well as retinoblastoma protein. In conclusion, the present results indicated a relevant impact of overexpression of MCPIP1 on the cell cycle, namely a block of the G1/S cell‐cycle checkpoint, resulting in arrest of NB cells in the G1 phase. Abstract : It was confirmed that ectopic overexpression of monocyte chemoattractant protein‐1‐induced protein (1MCPIP1) in two human NB cell lines, KELLY and BE(2)‐C inhibited the cell proliferation. Furthermore, it was demonstrated that MCPIP1 overexpression causes an accumulation of NB cells in the G1 phase of the cell cycle. Additionally, it was confirmed that MCPIP1 overexpression reduced the expression of certain cyclins and decreased the phosphorylation of various cyclin‐dependent kinases, as well as retinoblastoma protein. In conclusion, the present results indicate a relevant impact of MCPIP1 overexpression on the cell cycle, namely a block of the G1/S cell‐cycle checkpoint, resulting in G1‐phase arrest of NB cells