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WBP2 modulates G1/S transition in ER+ breast cancer cells and is a direct target of miR-206.
- Source :
-
Cancer Chemotherapy & Pharmacology . May2017, Vol. 79 Issue 5, p1003-1011. 9p. - Publication Year :
- 2017
-
Abstract
- <bold>Purpose: </bold>The mechanisms underlying the oncogenic properties of WW domain binding protein 2 (WBP2) in breast cancer have not been fully understood. In this study, we explored the role of WBP2 in cell cycle regulation in ER+ breast cancer cells and how it is regulated in the cancer cells.<bold>Methods: </bold>The association between WBP2 expression and prognosis in ER+ breast cancer was assessed by data mining in Breast Cancer Gene-Expression Miner v4.0. Cell cycle was assessed by PI staining and flow cytometry. EdU staining was applied to visualize cells in S phase. The binding between miR-206 and WBP2 were verified by dual luciferase assay. CCK-8 assay and flow cytometric analysis were applied to assess the functional role of WBP2 and miR-206 in the cancer cells.<bold>Results: </bold>High WBP2 expression correlates with higher risk of any events (AE) and metastatic relapse (MR) and also indicates shorter AE-free survival and MR-free survival in ER+ breast cancer patients. In both MCF-7 and BT474 cells, WBP can influence the expression of G1/S-related cell cycle proteins, including p21, CDK4, and cyclin D1. In addition, WBP2 overexpression resulted in facilitated G1/S transition, while WBP2 knockdown impaired the transition. The 3'UTR of WBP2 has a conserved miR-206 binding site. Functionally, miR-206 knockdown decreased tamoxifen sensitivity in tamoxifen-sensitive (TamS) MCF-7 cells, while miR-206 overexpression and WBP2 knockdown enhanced the sensitivity in tamoxifen-resistant (TamR) MCF-7 cells.<bold>Conclusion: </bold>Based on these findings, we infer that the miR-206/WBP2 axis can modulate tamoxifen sensitivity via regulating G1/S progression in ER+ breast cancer. [ABSTRACT FROM AUTHOR]
- Subjects :
- *BREAST cancer prognosis
*TARGETED drug delivery
*MICRORNA
*CARRIER proteins
*TAMOXIFEN
*BREAST cancer treatment
*GENETIC overexpression
*ANTINEOPLASTIC agents
*BINDING sites
*BREAST tumors
*CELL lines
*CELL physiology
*DRUG resistance in cancer cells
*GENETIC techniques
*PROGNOSIS
*PROTEINS
*RNA
*CELL cycle proteins
*PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 03445704
- Volume :
- 79
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Cancer Chemotherapy & Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 122654371
- Full Text :
- https://doi.org/10.1007/s00280-017-3302-0