LncRNA DILA1 inhibits Cyclin D1 degradation and contributes to tamoxifen resistance in breast cancer

Qianfeng Shi, Yudong Li, Shunying Li, Liang Jin, Hongna Lai, Yanqing Wu, Zijie Cai, Mengdi Zhu, Qian Li, Ying Li, Jingru Wang, Yujie Liu, Zongqi Wu, Erwei Song and Qiang Liu ()
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Qianfeng Shi: Sun Yat-Sen University
Yudong Li: Sun Yat-Sen University
Shunying Li: Sun Yat-Sen University
Liang Jin: Sun Yat-Sen University
Hongna Lai: Sun Yat-Sen University
Yanqing Wu: Sun Yat-Sen University
Zijie Cai: Sun Yat-Sen University
Mengdi Zhu: Sun Yat-Sen University
Qian Li: Sun Yat-Sen University
Ying Li: Sun Yat-Sen University
Jingru Wang: Sun Yat-Sen University
Yujie Liu: Sun Yat-Sen University
Zongqi Wu: Sun Yat-Sen University
Erwei Song: Sun Yat-Sen University
Qiang Liu: Sun Yat-Sen University

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Cyclin D1 is one of the most important oncoproteins that drives cancer cell proliferation and associates with tamoxifen resistance in breast cancer. Here, we identify a lncRNA, DILA1, which interacts with Cyclin D1 and is overexpressed in tamoxifen-resistant breast cancer cells. Mechanistically, DILA1 inhibits the phosphorylation of Cyclin D1 at Thr286 by directly interacting with Thr286 and blocking its subsequent degradation, leading to overexpressed Cyclin D1 protein in breast cancer. Knocking down DILA1 decreases Cyclin D1 protein expression, inhibits cancer cell growth and restores tamoxifen sensitivity both in vitro and in vivo. High expression of DILA1 is associated with overexpressed Cyclin D1 protein and poor prognosis in breast cancer patients who received tamoxifen treatment. This study shows the previously unappreciated importance of post-translational dysregulation of Cyclin D1 contributing to tamoxifen resistance in breast cancer. Moreover, it reveals the novel mechanism of DILA1 in regulating Cyclin D1 protein stability and suggests DILA1 is a specific therapeutic target to downregulate Cyclin D1 protein and reverse tamoxifen resistance in treating breast cancer.

Date: 2020
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DOI: 10.1038/s41467-020-19349-w

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