BMI-1 promotes breast cancer proliferation and metastasis through different mechanisms in different subtypes

BMI-1在不同亚型中通过不同机制促进乳腺癌增殖和转移

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作者:Jin-Yan Liu, Yan-Nan Jiang, Hai Huang, Jin-Fu Xu, Ying-Hui Wu, Qiang Wang, Yue Zhu, Bo Zheng, Cong Shen, Wei-Feng Qian, Jun Shen

Abstract

Breast cancer is among the most common malignant cancers in women. B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) is a transcriptional repressor that has been shown to be involved in tumorigenesis, the cell cycle, and stem cell maintenance. In our study, increased expression of BMI-1 was found in both human triple negative breast cancer and luminal A-type breast cancer tissues compared with adjacent tissues. We also found that knockdown of BMI-1 significantly suppressed cell proliferation and migration in vitro and in vivo. Further mechanistic research demonstrated that BMI-1 directly bound to the promoter region of CDKN2D/BRCA1 and inhibited its transcription in MCF-7/MDA-MB-231. More importantly, we discovered that knockdown of CDKN2D/BRCA1 could promote cell proliferation and migration after repression by PTC-209. Our results reveal that BMI-1 transcriptionally suppressed BRCA1 in TNBC cell lines whereas, in luminal A cell lines, CDKN2D was the target gene. This provides a reference for the precise treatment of different types of breast cancer in clinical practice.

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