Home Neoplasma 2018 Neoplasma Vol.65, No.5, p.693-700, 2018

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ISSN 0028-2685
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Neoplasma Vol.65, No.5, p.693-700, 2018

Title: Anticancer effect of YWHAZ silencing via inducing apoptosis and autophagy in gastric cancer cells
Author: F. GUO, D. JIAO, G.Q. SUI, L.N. SUN, Y.J. GAO, Q.F. FU, C.X. JIN

Abstract: 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 detailed and still require study. Herein, 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 the Bcl-2 level. Suppression of YWHAZ also promoted autophagy, confirmed by the up-regulation of LC3II /LC3I ratio, and down-regulation 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 effect. 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.

Keywords: YWHAZ; gastric cancer; apoptosis; autophagy; PI3K/AKT/mTOR
Published online: 24-Sep-2018
Year: 2018, Volume: 65, Issue: 5 Page From: 693, Page To: 700
doi:10.4149/neo_2018_170922N603
Price: 16.80 €






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