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

• Published in: Cancer science Vol. 114; no. 2; pp. 449 - 462
• Main Authors: Liu, Jin‐yan, Jiang, Yan‐nan, Huang, Hai, Xu, Jin‐fu, Wu, Ying‐hui, Wang, Qiang, Zhu, Yue, Zheng, Bo, Shen, Cong, Qian, Wei‐feng, Shen, Jun
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.02.2023; John Wiley and Sons Inc
• Subjects: Animals; Antibodies; Biotechnology; Bmi protein; BMI‐1; Body Mass Index; BRCA1; BRCA1 protein; Breast cancer; Cancer therapies; CDKN2D; Cell adhesion & migration; Cell cycle; Cell Line; Cell Line, Tumor; Cell migration; Cell proliferation; Cell Proliferation - genetics; Chemotherapy; Cyclin-dependent kinases; Female; Gene Expression Regulation, Neoplastic; histone modification; Humans; Kinases; Lymphocytes B; Metastases; Mice; Mortality; Original; Proteins; Stem cells; Transcription; Transcription Factors - genetics; Triple Negative Breast Neoplasms - metabolism; Tumorigenesis; Tumors; United States > US; China; CDKN2D; breast cancer; BRCA1; BMI-1; histone modification
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.15623

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. BMI‐1 promotes proliferation and migration via transcriptional inhibition of cyclin‐dependent kinase inhibitor 2D (CDKN2D) in luminal A‐type breast cancer but via transcriptional inhibition of breast cancer susceptibility gene 1 (BRCA1) in TNBC.