Decreased Sp1 Expression Mediates Downregulation of SHIP2 in Gastric Cancer Cells

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2017 Jan 25

PMID 28117748

Citations 5

Authors

Yan Ye

Xue Yi Qian

Miao Miao Xiao

Yu Ling Shao

Li Mei Guo

Dong Ping Liao

Jie Da

Lin Jie Zhang

Jiegou Xu

Affiliations

Soon will be listed here.

Abstract

Past studies have shown that the Src homology 2-containing inositol 5-phosphatase 2 (SHIP2) is commonly downregulated in gastric cancer, which contributes to elevated activation of PI3K/Akt signaling, proliferation and tumorigenesis of gastric cancer cells. However, the mechanisms underlying the reduced expression of SHIP2 in gastric cancer remain unclear. While gene copy number variation analysis and exon sequencing indicated the absence of genomic alterations of , bisulfite genomic sequencing (BGS) showed promoter hypomethylation of in gastric cancer cells. Analysis of transcriptional activity of promoter revealed Specificity protein 1 (Sp1) was responsible for the regulation of SHIP2 expression in gastric cancer cells. Furthermore, Sp1 expression, but not Sp3, was frequently downregulated in gastric cancer compared with normal gastric mucosa, which was associated with a paralleled reduction in SHIP2 levels in gastric cancer. Moreover, overexpression of Sp1 inhibited cell proliferation, induced apoptosis, suppressed cell motility and invasion in gastric cancer cells in vitro, which was, at least in part, due to transcriptional activation of mediated by Sp1, thereby inactivating Akt. Collectively, these results indicate that decreased expression of transcription factor Sp1 contributes to suppression of SHIP2 in gastric cancer cells.

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