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Int. J. Mol. Sci. 2017, 18(1), 220;

Decreased Sp1 Expression Mediates Downregulation of SHIP2 in Gastric Cancer Cells

Department of Immunology, Anhui Medical University, Hefei 230032, China
Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Academic Editors: William Chi-shing Cho and Terrence Piva
Received: 21 November 2016 / Revised: 22 December 2016 / Accepted: 15 January 2017 / Published: 22 January 2017
(This article belongs to the Section Biochemistry)
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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 SHIP2, bisulfite genomic sequencing (BGS) showed promoter hypomethylation of SHIP2 in gastric cancer cells. Analysis of transcriptional activity of SHIP2 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 SHIP2 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. View Full-Text
Keywords: gastric cancer; SHIP2; Sp1 gastric cancer; SHIP2; Sp1

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Ye, Y.; Qian, X.Y.; Xiao, M.M.; Shao, Y.L.; Guo, L.M.; Liao, D.P.; Da, J.; Zhang, L.J.; Xu, J. Decreased Sp1 Expression Mediates Downregulation of SHIP2 in Gastric Cancer Cells. Int. J. Mol. Sci. 2017, 18, 220.

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