NCAPG Promotes The Proliferation Of Hepatocellular Carcinoma Through The CKⅡ-dependent Regulation Of PTEN

Objective: NCAPG,non-SMC subunit in the concentrate I complex,might be promoting the proliferation of hepatocellular carcinoma(HCC),but the mechanism was unclear.The aim of this study was to explore how NCAPG affects PTEN to influence the proliferation of HCC.Methods: The expression of NCAPG in HCC and its adjacent tissues was analyzed by Oncomine database.The expression of NCAPG in HCC and adjacent tissues was verified by Western blot.Establishment of a nude mouse model of human hepatocellular carcinoma to evaluate the effect of NCAPG on the growth of HCC cells in vivo.Transcriptome sequencing was used to discover the relationship between NCAPG and PTEN.The protein-protein interaction between NCAPG and CK II was studied by proteomic sequencing and co-precipitation(Co-IP)techniques.High and low expression cell models of NCAPG were constructed in HCC cell lines MHCC-97 H and HCC-lm3.The effects of NCAPG on the proliferation of HCC cells were studied by immunoblotting,Edu,CCK-8 and plate cloning.Using PI3K-AKT pathway inhibitor MK2206,the effects of NCAPG on the proliferation of liver cancer and PTEN were studied by immunoblotting,EDU,CCK-8 and plate cloning experiments.The relationship between NCAPG and CK II,PTEN was studied by western blotting in the cells with high expression of NCAPG and those with low expression of NCAPG.Results: The expreiment confirmed that NCAPG was abnormally overexpressed in HCC and promoted the proliferation of HCC cells.Transcriptome sequencing revealed that NCAPG inhibited the transcription of PTEN and promoted the PI3K-AKT pathway.A close association between NCAPG and CKⅡhas been found through proteomic sequencing;their interaction was confirmed by Co-IP.There was a positive correlation between NCAPG and CKⅡ that promoted the phosphorylation of PTEN and thus inhibited the transcription and functions of PTEN.We also proved that CKⅡ was the key for proliferation caused by NCAPG.Conclusion: The experiment reveal the mechanism by which NCAPG regulates the proliferation of HCC: NCAPG inhibits PTEN through its interaction with CKⅡ,and then activates the PI3K-AKT pathway to promote proliferation of HCC.