Identification of BAP18 as a Novel ER Target Gene and Its Function in ER Positive Breast Cancer

WANG Anqi¹, LI Jiaxuan¹, ZHANG Bohan², LIN Lin³, SUN Ge³*

(¹The First Department of Clinical Medicine, China Medical University, Shenyang 110122, China; ²The Third Department of Clinical Medicine, China Medical University, Shenyang 110122, China; ³Department of Cell Biology, Key Laboratory of Medical Cell Biology, Ministry of Education, School of Life Sciences, China Medical University, Shenyang 110122, China)

Abstract:

ER (estrogen receptor) and E2 (estradiol) play crucial roles in the occurrence and development of breast cancer, which regulate the transcription and protein expression of their downstream target genes. Identification of new ER downstream target genes provides new therapeutic targets for the clinical treatment of breast cancer. This study identified a novel ER downstream target gene BAP18 in ER-positive breast cancer cells by Western blot and qPCR assays. The BAP18 expression could be up-regulated by E2 and ER, while its expression decreased following antiestrogens such as tamoxifen or fluvestrant. Potential ER binding sites were identified upon the promoter region of BAP18. After the construction of luciferase plasmids to detect BAP18 transcriptional activity, luciferase assays and ChIP assays confirmed the ER binding site and the activation region. The EMSA assay confirmed that ER could directly bind to the promoter region of BAP18. Finally, targeting by CRISPR-Cas9, it was found that BAP18 knockdown could slow the growth and proliferation and increase the apoptosis of ER positive breast cancer cells. This study identified BAP18 as a newly discovered downstream target gene of ER, which plays a vital role in breast cancer. The discovery of BAP18 is expected to provide a theoretical basis and a new therapeutic target for the clinical treatment of ER positive breast cancer.

CSTR: 32200.14.cjcb.2021.07.0015