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MTA2 promotes gastric cancer cells invasion and is transcriptionally regulated by Sp1.

ABSTRACT: BACKGROUND: MTA2 gene belongs to metastasis associated family, and is highly expressed in some solid tumors, including gastric cancer. Its biological function in gastric cancer is currently undefined. METHODS: Metastasis-associated tumor gene family 2 (MTA2) and transcription factor specificity protein 1 (Sp1) expression were detected in 127 gastric cancer samples by immunohistochemistry staining. SGC-7901 and AGS gastric cancer cell lines transfected by MTA2 shRNA was used for biological function investigation. Binding and regulation activities of Sp1 on MTA2 promoter were investigated by chromatin immunoprecipitation and luciferase reporter gene. RESULTS: The expression rate of MTA2 in gastric cancer tissues was 55.9% (71/127), and its expression was closely related to the depth of tumor invasion, lymph nodes metastasis, and TNM staging. MTA2 knockdown in human SGC-7901 and AGS gastric cancer cells significantly inhibited migration and invasion in vitro, and disrupted structure of cytoskeleton. MTA2 knockdown also attenuated xenografts growth and lung metastasis in nude mice model. MTA2 expression was positively correlated with transcription factor Sp1 in gastric cancer tissues (r = 0.326, P < 0.001). Sp1 bound to human MTA2 gene promoter at region from -1043 bp to -843 bp. Transcriptional activity of MTA2 promoter could be enhanced by Sp1 overexpression. CONCLUSIONS: MTA2 knockdown impairs invasion and metastasis of gastric cancer cells, and attenuates xenografts growth in vivo. Sp1 regulates MTA2 expression at transcriptional level.

SUBMITTER: Zhou C

PROVIDER: S-EPMC3851872 | biostudies-other | 2013

REPOSITORIES: biostudies-other

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MTA2 promotes gastric cancer cells invasion and is transcriptionally regulated by Sp1.

Zhou Chenfei C Ji Jun J Cai Qu Q Shi Min M Chen Xuehua X Yu Yingyan Y Liu Bingya B Zhu Zhenggang Z Zhang Jun J

Molecular cancer 20130908 1

<h4>Background</h4>MTA2 gene belongs to metastasis associated family, and is highly expressed in some solid tumors, including gastric cancer. Its biological function in gastric cancer is currently undefined.<h4>Methods</h4>Metastasis-associated tumor gene family 2 (MTA2) and transcription factor specificity protein 1 (Sp1) expression were detected in 127 gastric cancer samples by immunohistochemistry staining. SGC-7901 and AGS gastric cancer cell lines transfected by MTA2 shRNA was used for biol ...[more]

PMID: 24010737

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Project description:ObjectiveThis study aims to investigate the expression, role, and detailed mechanism of microRNA-204-5p and zinc finger protein 521 in gastric cancer.MethodsImmunohistochemistry was adopted to detect the expressions of zinc finger protein 521 in 82 cases of gastric cancer tissues. Western blot was used to detect the expressions of zinc finger protein 521 in gastric cancer cells and adjacent cells. Moreover, the correlation between zinc finger protein 521 and the prognosis of patients were also evaluated. Cell Counting Kit 8 assay and colony formation assay were performed to figure out the impact of zinc finger protein 521 on the proliferation of gastric cancer cells. By conducting flow cytometry, the effect of zinc finger protein 521 on the apoptosis of gastric cancer cells was determined. The scratch wound healing assay and transwell invasion assay were carried out to determine the effect of zinc finger protein 521 on regulating the motility and invasion of gastric cancer cells. Ultimately, the targeting relationship and interaction between microRNA-204-5p and zinc finger protein 521 were verified by real-time polymerase chain reaction, Western blot, and dual luciferase reporter gene assay.ResultsCompared with adjacent cells, zinc finger protein 521 was highly expressed in gastric cancer cells, which was related to TNM stage (P = .0388), tumor size (P = .0168), and local lymph node metastasis (P = .0024). Overexpressed zinc finger protein 521 can promote the proliferation, migration, and invasion of gastric cancer cells and inhibit the apoptosis. Zinc finger protein 521 is a target gene of microRNA-106-5p, and there was a negative correlation between the expression of zinc finger protein 521 and microRNA-204-5p.ConclusionZinc finger protein 521 can arrest the apoptosis and enhance the proliferation, migration, and invasion of gastric cancer cells via regulating microRNA-204-5p. Our study may provide novel clues for the treatment of patients with gastric cancer.

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MTA2 promotes gastric cancer cells invasion and is transcriptionally regulated by Sp1.

Publications

MTA2 promotes gastric cancer cells invasion and is transcriptionally regulated by Sp1.

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