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SPAG5 Activates PI3K/AKT Pathway and Promotes the Tumor Progression and Chemo-Resistance in Gastric Cancer.

Authors :
An, Juan
Yang, Lang
Pan, Yuanming
He, Yuqi
Xie, Hui
Tao, Yurong
Li, Wei
Yan, Yupeng
Chen, Siai
Liu, Ya
Ma, Xiaoming
An, Ling
Ji, Dongde
Su, Zhanhai
Sheng, Jianqiu
Source :
DNA & Cell Biology; Oct2022, Vol. 41 Issue 10, p893-902, 10p
Publication Year :
2022

Abstract

The sperm-associated antigen 5 (SPAG5) is an important protein in mitosis and cell cycle checkpoint regulation, with more attention as a novel oncogene in various cancers. High level of SPAG5 expression has been detected in our clinical gastric cancer (GC) samples and The Cancer Genome Atlas GC data. However, the bio-function and potential mechanism of SPAG5 in GC remain unclear. In this study, we investigated the role of SPAG5 in GC development and the correlation between SPAG5 and 5-fluorouracil (5-FU) treatment. SPAG5 expression was increased in GC samples compared with that in normal tissues (80.8% vs. 22.0%), which was apparently associated with a worse outcome. Biological experiments showed that knockdown of SPAG5 induced apoptosis and suppressed proliferation in cells and animal models. Downregulation of SPAG5 enhanced the sensitivity of 5-FU in GC cells. Gene microarray chip identified 856 upregulated and 787 downregulated genes in SPAG5 silencing cells. Furthermore, 12 significant genes, including CDKN1A, CDKN1B, EIF4E, MAPK1, and HSP90B1, belonged to the PI3K/AKT signaling pathway using ingenuity pathway analysis. Meanwhile, real-time PCR and Western blotting results showed that knockdown of SPAG5 inhibited PI3K/AKT signaling pathway. Collectively, SPAG5 promotes the growth of GC cells by regulating PI3K/AKT signaling pathway, which could be the promising target gene in GC therapy. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
10445498
Volume :
41
Issue :
10
Database :
Complementary Index
Journal :
DNA & Cell Biology
Publication Type :
Academic Journal
Accession number :
159794382
Full Text :
https://doi.org/10.1089/dna.2021.0531