| Objective:Coiled-coil domain containing 106 protein(CCDC106)enhances tumor cell proliferation primarily by promoting p53 degradation.Recent studies show that CCDC106 is involved in regulating invasion and proliferation via a p53-independent pathway.In this study,we sought to characterize the mechanism of action of CCDC106 in this processMethods:CCDC106 expression patterns and subcellular distribution in ovarian cancer cells SKOV3,CAOV3,OVCAR3,and A2780 were evaluated by immunofluorescence and Western blot analysis.Based on the expression patterns,the relationship between the localization of CCDC106 and its function was analyzed with CCK8 assays,soft agar colony formation assays,transwell experiments,and WB analysis.A CK2 kinase inhibitor was used to block the nuclear translocation of CCDC106 to further analyze the association between its localization and function.ATF4,a potential co-effector of CCDC106,was identified by database comparison analysis and mass spectrometry analysis.A luciferase reporter gene construct and real-time polymerase chain PCR were used to analyze the interaction of ATF4 and CCDC106,and the effect of their interaction on the cell cycle regulator,P21Results:The nuclear translocation of CCDC106 is critical for its biological function.After CCDC106 enters the nucleus,it can regulate various cellular activities through both P53-dependent and P53-independent pathways.In P53(-)cell lines,we found that CCDC106 inhibited the transcription of P21 by binding to ATF4,negative control P21and P27,thus stimulatingtheproliferationof tumor cells.Moreover,CCDC106 promoted tumor cell invasion by regulating epithelial-mesenchymal transition-related factorsConclusion:CCDC106 strengthens the suppression of ATF4 on the transcription of p21/p27 in a p53 non-dependent pathway and promotes the proliferation.Our findings suggest that CCDC106 may provide a potential therapeutic target of ovarian cancer for therapeutic target and basic. |
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