NCAPG Promotes The Proliferation Of Hepatocellular Carcinoma Through PI3K/AKT Signaling
Authors Gong C, Ai J, Fan Y, Gao J, Liu W, Feng Q, Liao W, Wu L
Received 31 May 2019
Accepted for publication 26 September 2019
Published 16 October 2019 Volume 2019:12 Pages 8537—8552
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Sanjay Singh
Chengwu Gong,1,* Jiyuan Ai,1,* Yun Fan,2 Jun Gao,1 Weiwei Liu,1 Qian Feng,3 Wenjun Liao,1 Linquan Wu1
1Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of China; 2Department of Neurology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430000, People’s Republic of China; 3Department of Emergency Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Linquan Wu; Wenjun Liao
Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang 330006, People’s Republic of China
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Purpose: Studies show that high expression of non-SMC condensin I complex subunit G (NCAPG) is associated with many tumors. In this study, we explore the mechanism by which NCAPG promotes proliferation in hepatocellular carcinoma (HCC).
Patients and methods: Liver cancer and paracancerous tissue specimens of 90 HCC patients were collected, and expression levels of NCAPG in these tissues and cell lines were evaluated by Western blotting and immunohistochemistry. HCC cells were transfected with siRNAs and plasmids, and pathway activators or inhibitors were added. The 5-ethynyl-2ʹ-deoxyuridine (EdU) proliferation assay was used to measure cell proliferation. Flow cytometry was used to evaluate cell apoptosis. Western blot assays were performed as a standard procedure to detect total protein expression. Treated HCC cells were subcutaneously injected into nude mice.
Results: Analysis using the Oncomine database showed that NCAPG was upregulated in HCC and immunohistochemistry and Western blot assays showed it was upregulated in both HCC tissues and HCC 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 a role in the HCC via PI3K-AKT signaling pathway. The PI3K/AKT/FOXO4 pathway was aberrantly activated, and the expressions of apoptosis-related protein were altered when NCAPG was overexpressed or silenced both in vitro and in vivo. LY294002, a PI3K inhibitor, could eliminate the NCAPG role of promoting HCC cell proliferation and reducing HCC cell apoptosis, while 740Y-P, a PI3K activator, contributed to the opposite effect.
Conclusion: NCAPG functions as an oncogene in HCC and plays a role in promoting cell proliferation and antiapoptosis through activating the PI3K/AKT/FOXO4 pathway.
Keywords: NCAPG, hepatocellular carcinoma, PI3K/AKT, FOXO4, proliferation
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