<p>NCAPG Promotes The Proliferation Of Hepatocellular Carcinoma Through PI3K/AKT Signaling</p>

Abstract

PurposeStudies 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 methodsLiver 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.ResultsAnalysis 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.ConclusionNCAPG functions as an oncogene in HCC and plays a role in promoting cell proliferation and antiapoptosis through activating the PI3K/AKT/FOXO4 pathway.

Identification of Hub Genes Associated With Hepatocellular Carcinoma Using Robust Rank Aggregation Combined With Weighted Gene Co-expression Network Analysis

“…Significantly, AKR1B10 was not included in the GSE84005 dataset or NCAPG and LAPTM4B in the GSE45114 dataset. However, close association of these three genes with the progression of HCC has been recently reported ( DiStefano and Davis, 2019 ; Gong et al, 2019 ; Wang F. et al, 2019 ). The RRA method effectively maximizes the retention of hub genes.…”

“…For example, as shown in Figure 1B , AKR1B10, NCAPG, and LAPTM4B exist in multiple datasets and would therefore be lost if the datasets were simply merged. However, these genes are closely related to the progression of HCC ( DiStefano and Davis, 2019 ; Gong et al, 2019 ; Wang F. et al, 2019 ). Furthermore, in dataset GSE39791, logFC values of some of the top 20 DEGs were less than 1.…”

NCAPG confers trastuzumab resistance via activating SRC/STAT3 signaling pathway in HER2-positive breast cancer

“…It was previously found that NCAPG promotes proliferation, metastasis, and recurrence in HCC 12 . RNA sequencing revealed that overexpression of NCAPG can induce cell proliferation and inhibit apoptosis via activation of the PI3K-AKT signaling pathway in HCC 17 . Upregulated NCAPG also correlated positively with the cell proliferation and poor survival in BC as well as the poor disease-free survival and advanced clinical stage in castration-resistant prostate cancer 14 , 18 , 19 .…”

“…Upregulation of NCAPG has been suggested to facilitate cell proliferation in gastric cancer 15 . Moreover, ectopic NCAPG was shown to promote cell proliferation, metastasis, differentiation in HCC and was associated with poor TNM stages, poor survival, and tumor recurrence in HCC patients 16,17 . Although NCAPG has previously been reported to be overexpressed and correlated with poor survival in BC 18,19 , its biological role and mechanism have not been explored.…”

Revelation of critical genes and pathways involved in hepatocellular carcinoma (HCC) and phylogenetic tree construction of CDK1 protein family An integrated multi-omics bioinformatics analysis

“…In terms of enhancing the proliferation of HCC, NCAPG shares similar mechanisms with TTK. NCAPG, which is also called non-SMC condensin I complex subunit G, and the overexpression of NCAPG leads to an enhanced proliferation and reduced apoptosis of HCC through PI3K/AKT signaling pathway (52) Ying et al .in 2018 (54) reported that ZWINT promotes the proliferation of HCC through the regulation of cell-cycle-related proteins such as CDK1, PCNA, etc. The regulation is also mentioned in the top ten hub gene network, which is corresponding to our ndings.…”