Dataset Information

MTA1, a Target of Resveratrol, Promotes Epithelial-Mesenchymal Transition of Endometriosis via ZEB2.

ABSTRACT: Endometriosis is a benign disease that shares some malignant features. Epithelial-mesenchymal transition (EMT) is involved in the pathogenesis of endometriosis. Metastasis-associated protein 1 (MTA1) plays an important role in various cancers by promoting EMT, yet there are no studies on its function in endometriosis. In the present study, we found that MTA1 was highly expressed in the ectopic endometrium of endometriosis patients and that the expression of MTA1 was related to the revised American Fertility Society stage. MTA1 facilitated endometrial stroma cell proliferation, migration, and invasion by inducing EMT, and the promotion function and MTA1 expression were suppressed by resveratrol, a natural polyphenol. Moreover, we revealed that MTA1 induced EMT through interaction with ZEB2. The findings in a mouse endometriosis model further showed that MTA1 and ZEB2 were upregulated in ectopic tissues and that resveratrol inhibited the growth of ectopic lesions and expression of MTA1 and ZEB2. Taken together, we demonstrate that MTA1 is a protein that promotes EMT via interacting with ZEB2 in the pathogenesis of endometriosis, and may be a target of resveratrol.

SUBMITTER: Kong X

PROVIDER: S-EPMC7578554 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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MTA1, a Target of Resveratrol, Promotes Epithelial-Mesenchymal Transition of Endometriosis via ZEB2.

Kong Xiangyi X Xu Xiaofeng X Zhou Ling L Zhu Mengjing M Yao Shuang S Ding Yue Y Liu Tao T Wang Yijin Y Zhang Yan Y Li Rong R Tang Xiaoqiu X Ling Jingxian J Wu Jun J Zhu Xianghong X Gu Yuanyuan Y Zhou Huaijun H

Molecular therapy. Methods & clinical development 20200928

Endometriosis is a benign disease that shares some malignant features. Epithelial-mesenchymal transition (EMT) is involved in the pathogenesis of endometriosis. Metastasis-associated protein 1 (MTA1) plays an important role in various cancers by promoting EMT, yet there are no studies on its function in endometriosis. In the present study, we found that MTA1 was highly expressed in the ectopic endometrium of endometriosis patients and that the expression of MTA1 was related to the revised Americ ...[more]

PMID: 33145366

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Project description:BackgroundSeveral members of the tripartite motif-containing (TRIM) protein family have been reported to serve as vital regulators of tumorigenesis. Recent studies have demonstrated an oncogenic role of TRIM 14 in multiple human cancers; however, the importance of this protein in glioblastoma remains to be elucidated.MethodsThe expression levels of TRIM14 were analyzed in a series of database and were examined in a variety of glioblastoma cell lines. Two independent TRIM14 shRNA were transfected into LN229 and U251 cells, and the effect of TRIM14 depletion was confirmed. Transwell assay and wound healing assay assay were carried out to assess the effect of TRIM14 depletion on glioblastoma cell invasion and migration. Western blotting was performed to screen the downstream gene of TRIM14. The stability analysis and Ubiquitylation assays and Orthotopic xenograft studies were also performed to investigate the role of TRIM14 and the relationship with downstream gene. Human glioblastoma tissues were obtained and immunohistochemical staining were carried out to confirm the clinical significance of TRIM14.ResultsIn this study, we showed that TRIM14 was upregulated in human glioblastoma specimens and cell lines, and correlated with glioblastoma progression and shorter patient survival times. Functional experiments showed that decreased TRIM14 expression reduced glioblastoma cell invasion and migration. Furthermore, we identified that zinc finger E-box binding homeobox 2 (ZEB2), a transcription factor involved in epithelial-mesenchymal transition, is a downstream target of TRIM14. Further investigation revealed that TRIM14 inactivation significantly facilitated ZEB2 ubiquitination and proteasomal degradation, which led to aggressive invasion and migration. Our findings provide insight into the specific biological role of TRIM14 in tumor invasion.ConclusionsOur findings provide insight into the specific biological role of TRIM14 in tumor invasion, and suggest that targeting the TRIM14/ZEB2 axis might be a novel therapeutic approach for blocking glioblastoma.

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Dataset Information

MTA1, a Target of Resveratrol, Promotes Epithelial-Mesenchymal Transition of Endometriosis via ZEB2.

Publications

MTA1, a Target of Resveratrol, Promotes Epithelial-Mesenchymal Transition of Endometriosis via ZEB2.

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