Open AccessNET1 promotes HCC growth and metastasis in vitro and in vivo via activating the Akt signaling pathway
Author(s) -
Zhenhua Chen,
QianZhi Ni,
Xiuping Zhang,
Ning Ma,
Jing-Kai Feng,
Kang Wang,
Jingjing Li,
Dong Xie,
Xiaochun Ma,
Shuqun Cheng
Publication year - 2021
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.202845
Subject(s) - in vivo , protein kinase b , in vitro , cancer research , metastasis , pi3k/akt/mtor pathway , signal transduction , microbiology and biotechnology , chemistry , biology , medicine , cancer , biochemistry , genetics
Neuroepithelial cell transforming gene 1 (NET1), a member of the guanine nucleotide exchange factor family, is involved in various cancers, including gastric cancer, breast cancer and glioma. However, the role of NET1 in hepatocellular carcinoma (HCC) remains largely uncovered. In this study, we found that NET1 expression was upregulated in HCC, and that upregulated NET1 expression was closely associated with poor prognosis and some clinical characteristics in HCC patients. Whilst forced expression of NET1 in HCC cells was observed to significantly promote cell growth and metastasis in vitro and in vivo ; downregulation of NET1 was shown to exhibit an opposite inhibitory effect. RNA-seq analysis and gene set enrichment analysis demonstrated that knockdown of NET1 significantly suppressed the level of Akt phosphorylation level and the expression of Akt downstream genes in HCC cells. Moreover, MK2206, a potent Akt inhibitor was shown to block the NET1-induced effects in HCC. Taken together, this study demonstrated that, through the Akt signaling pathway, NET1 plays an oncogenic role in HCC progression and metastasis. Hence, NET1 may potentially be used as a potential therapeutic target and prognostic marker of HCC.