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WBP2 modulates G1/S transition in ER+ breast cancer cells and is a direct target of miR-206

Cancer Chemotherapy and Pharmacology volume 79, pages 1003–1011 (2017)Cite this article

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

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Affiliations

  1. Clinical Laboratory, Linyi Central Hospital, Linyi, 276400, Shandong, China

    Yong-qiang Ren

  2. Department of Breast and Thyroid Surgery, People’s Hospital of Rizhao, Rizhao, 276800, Shandong, China

    Hui-jun Wang

  3. Department of Breast Surgery, Weifang People’s Hospital, Weifang, 261041, Shandong, China

    Yong-qing Zhang

  4. Breast Center, Shandong Cancer Hospital and Institute, Jinan, 250017, Shandong, China

    Yan-bing Liu

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  1. Yong-qiang Ren
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Correspondence to Yan-bing Liu.

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Cite this article

Ren, Yq., Wang, Hj., Zhang, Yq. et al. WBP2 modulates G1/S transition in ER+ breast cancer cells and is a direct target of miR-206. Cancer Chemother Pharmacol 79, 1003–1011 (2017). https://doi.org/10.1007/s00280-017-3302-0

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  • DOI: https://doi.org/10.1007/s00280-017-3302-0

Keywords

  • MiR-206
  • WBP2
  • G1/S
  • ER+
  • Breast cancer