title: Decreased Sp1 Expression Mediates Downregulation of SHIP2 in Gastric Cancer Cells.
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 ofSHIP2, bisulfite genomic sequencing (BGS) showed promoter hypomethylation ofSHIP2in gastric cancer cells. Analysis of transcriptional activity ofSHIP2promoter 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 ofSHIP2mediated 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.
authors.affiliation: Department of Immunology, Anhui Medical University, Hefei 230032, China. yeyan@ahmu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Immunology, Anhui Medical University, Hefei 230032, China. 18756907022@163.com.
authors.forename: Xue Yi
authors.initials: XY
authors.lastname: Qian
authors.affiliation: Department of Immunology, Anhui Medical University, Hefei 230032, China. 18226603096@163.com.
authors.forename: Miao Miao
authors.initials: MM
authors.lastname: Xiao
authors.affiliation: Department of Immunology, Anhui Medical University, Hefei 230032, China. 15955118431@163.com.
authors.forename: Yu Ling
authors.initials: YL
authors.lastname: Shao
authors.affiliation: Department of Immunology, Anhui Medical University, Hefei 230032, China. 15755161243@163.com.
authors.forename: Li Mei
authors.initials: LM
authors.lastname: Guo
authors.affiliation: Department of Immunology, Anhui Medical University, Hefei 230032, China. liaodp2009@163.com.
authors.forename: Dong Ping
authors.initials: DP
authors.lastname: Liao
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China. dajie213@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Da
authors.affiliation: Department of Immunology, Anhui Medical University, Hefei 230032, China. zlj33@ahmu.edu.cn.
authors.forename: Lin Jie
authors.initials: LJ
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Anhui Medical University, Hefei 230032, China. xujiegou@ahmu.edu.cn.
authors.forename: Jiegou
authors.initials: J
authors.lastname: Xu
mesh_terms: D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation / Q000235:genetics; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D016329:Sp1 Transcription Factor; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
keywords: SHIP2; Sp1; gastric cancer