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Oncotarget. 2017 Oct 31;8(60):102119-102133. doi: 10.18632/oncotarget.22183. eCollection 2017 Nov 24.

MiR-29b/TET1/ZEB2 signaling axis regulates metastatic properties and epithelial-mesenchymal transition in breast cancer cells.

Author information

1
The First Bethune Hospital, Jilin University, Changchun, Jilin 130021, China.
2
College of Veterinary Medicine, Jilin University, Changchun, Jilin 130062, China.
3
College of Animal Science, Jilin University, Changchun, Jilin 130062, China.
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Contributed equally

Abstract

MiR-29b has been reported to be both a suppressor and a promoter in breast cancer (BC) cells proliferation and metastasis. Significant efforts have been made to explain the seemingly contradictory effects of miR-29b on BC, but no answer has yet been clearly verified. In this study, we overexpressed and knocked down miR-29b in BC cell lines, modulated expression of its downstream target gene TET1 and downregulated a downstream target gene of TET1, ZEB2, to explore the regulatory mechanism of miR-29b in BC cell proliferation, migration and epithelial-mesenchymal transition (EMT). Our results showed lower expression of miR-29b in BC samples and cell lines. Functional assays showed that miR-29b overexpression resulted in a higher cell proliferation, greater colony formation, higher migration rate and EMT. A dual luciferase assay identified TET1 as a direct target of miR-29b. As the promoting effects of miR-29b in the proliferation and metastasis of MDA-MB-231 and MCF-7, knockdown of TET1 also led to increased proliferation, colony formation, invasion and EMT. Further, we found that TET1 bound to the promoter of ZEB2, and siTET1 enhanced ZEB2 expression. Disruption of ZEB2 expression inhibited BC cells proliferation, colony formation and invasion. Our results establish the miR-29b/TET1/ZEB2 pathway in BC cell proliferation, migration and provide a theoretical basis for further research on the molecular mechanisms and new clinical treatments for BC.

KEYWORDS:

MiR-29b; TET1; ZEB2; breast cancer; metastasis

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no potential conflicts of interest.

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