Open AccessNKAP plays an oncogenic function partly through AKT signaling pathway in hepatocellular carcinoma
Author(s) -
Tao Song,
J Y Liu,
Jiamei Yang
Publication year - 2019
Publication title -
neoplasma
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.628
H-Index - 50
eISSN - 1338-4317
pISSN - 0028-2685
DOI - 10.4149/neo_2018_181212n957
Subject(s) - gene knockdown , protein kinase b , cancer research , pi3k/akt/mtor pathway , signal transduction , apoptosis , cell growth , cyclin d1 , biology , downregulation and upregulation , viability assay , microbiology and biotechnology , chemistry , cell cycle , gene , biochemistry , genetics
NF-kB activating protein (NKAP) is a highly conserved protein involved in transcriptional repression, immune cell development, maturation, T cell acquisition of functional competency and maintenance of hematopoiesis. Here we first explore the function of NKAP in hepatocellular carcinoma (HCC). We found that NKAP was highly expressed in HCC tissues and associated with a poor patient survival. CCK8 assay showed that NKAP knockdown significantly decreased cell viability of HuH7 and Hep3B HCC cell lines. Cell invasion, tested by transwell assays, was significantly inhibited by NKAP knockdown in HuH7 and Hep3B cells (P<0.05). Percentage of cell apoptosis was significantly increased by NKAP knockdown in HuH7 cells (6.5% to 12.5%) and in Hep3B cells (8.3% to 27.3%). Furthermore, western blot results indicated that NKAP silence upregulated the expression of pro-apoptotic proteins Bax and Caspase3-P17 while downregulated anti-apoptotic protein Bcl2. Finaly, AKT signaling pathway was evaluated to reveal the underlying mechanism of NKAP in HCC cells. It was suggested that NKAP knockdown decreased the phosphorylation level of AKT and the expression of its downstream members p70S6K and Cyclin D1. Furthermore, we demonstrated that NKAP knockdown also played an oncogenic role in human gastric cancer AGS and MKN45 cells. In conclusion, for the first time our study reveals that NKAP promotes the proliferation and invasion in HCC cell lines at least partly through AKT signaling pathway.