Open AccessAnticancer effect of YWHAZ silencing via inducing apoptosis and autophagy in gastric cancer cells
Author(s) -
Feng Guo,
D Jiao,
Guoqing Sui,
Lei Sun,
Yu Gao,
Qiang Fu,
Chunxiang Jin
Publication year - 2018
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_170922n603
Subject(s) - pi3k/akt/mtor pathway , gene silencing , autophagy , downregulation and upregulation , protein kinase b , cancer research , ly294002 , small hairpin rna , apoptosis , microbiology and biotechnology , biology , chemistry , signal transduction , gene knockdown , biochemistry , gene
YWHAZ (14-3-3ζ) has been reported to be a prognostic marker for various tumors and play a crucial role in many oncogenic processes, including proliferation, migration and invasion. However, the functional role and mechanism of YWHAZ in gastric cancer (GC) are not in detail and still remain to be studied. In the present study, the endogenous expression of YWHAZ in gastric cancer cell line BGC-823 was silenced by YWHAZ-specific short hairpin RNA (shRNA). Our data showed that YWHAZ silencing resulted in cell cycle arrest in BGC-823 cells. Further, YWHAZ-silenced BGC-823 cells acquired increased apoptosis rate, which was confirmed by increased levels of cleaved caspase-3, cleaved PARP, and Bax, and decreased level of Bcl-2. Suppression of YWHAZ also promoted autophagy, confirming by the upregulation of LC3II /LC3I ratio, and downregulation of p62 level. Moreover, YWHAZ suppression inhibited the activation of PI3K/AKT/mTOR signaling pathway in BGC-823 cells. LY294002 (PI3K/AKT inhibitor, 200 nM) further promoted YWHAZ silencing-induced apoptosis and autophagy in BGC-823 cells, while insulin-like growth factor-1 (IGF-1; PI3K/AKT agonist, 10 ng/ml) had the opposite role. Finally, suppression of YWHAZ inhibited the growth of the xenograft tumor in vivo. This study provides extended evidence that YWHAZ can be a potential therapeutic target for GC.