Non-SMC Condensin I Complex Subunit G Promotes The Proliferation Of Hepatocellular Carcinoma Via PI3K/AKT/FOXO4 Signaling Axis

Objective:Non-SMC condensin I complex subunit G(NCAPG)is a mitotic-associated chromosomal condensed protein that is one of the non-SMC subunits present in the Concentrate I complex.In this research,we investigated the effects of NCAPG on the proliferation and apoptosis of hepatocellular carcinoma cell lines,and determined the specific mechanism of NCAPG in HCC,thus establishing that NCAPG as a prognostic biomarker and therapeutic target for potential therapy.Methods:The expression of NCAPG in HCC and its relationship with prognosis were analyzed by database.The expression of NCAPG in HCC tissues and cell lines were evaluated by immunohistochemistry(IHC)and Western blotting.NCAPG overexpr-ession of HCC cell models were constructed in SMMC-7721 and MHCC-97 H cells with plasmid.Silencing NCAPG expression in two HCC cell lines Huh-7 and HCC-LM3 cells with small interfering RNA.The effects of NCAPG on proliferation and apoptosis of HCC were examined by EdU proliferation assay and flow cytometry and the expression of Phosphatidylinositol 3-kinase,PI3K)/protein kinase B(PBT,AKT)pathway and FOXO4 were evaluated by Western blotting.Moreover,it was observed whether the addition of PI3K/AKT signaling pathway activators and inhibitors could reduce or restore the effects of NCAPG.Results:NCAPG expression was up-regulated in hepatocellular carcinoma(HCC)(563samples,P=1.48E-11)based on a meta-analysis of Oncomine database.We further confirmed that NCAPG was frequently up-regulated in HCC tissues and cell lines.The overexpression of NCAPG could promote HCC cell proliferation and reduce HCC cell apoptosis.More importantly,RNA-sequencing analysis predicted that NCAPG plays its roles in HCC via PI3K-AKT signaling pathway.PI3K/AKT/FOXO4 pathway was aberrantly activated and the expressions of apoptosis relatedprotein were altered when NCAPG were overexpressed or silenced both in vitro and in vivo.LY294002,a PI3 K inhibitor,could eliminate the NCAPG role of promoting HCC cell proliferation and reducing HCC cell apoptosis,while 740Y-P,a PI3 K activator,contributed to the opposite effect.Conclusion:NCAPG play a very important oncogenic role in HCC pathogenesis and progression by activating PI3K/AKT/FOXO4 signaling pathway.Thus,we consider that NCAPG may act as a biomarker for the prognosis and a potential therapeutic target for the gene treatment of HCC.