TRIM8 inhibits breast cancer proliferation by regulating estrogen signaling.

ABSTRACT: Breast cancer (BC) is the most common female malignancy worldwide, and 70% of which are estrogen receptor ? (ER?) positive. Endocrine treatment, such as tamoxifen, is a primary adjuvant therapy for patients with ER-positive BC. However, some patients will develop acquired resistance following long-time treatment. Further research on estrogen signaling is important to improve the therapy of these patients. In this study, we report that the E3 ubiquitin ligase tripartite motif 8 (TRIM8) acts as a novel regulator of ER? signaling. TRIM8 is downregulated in BC and is associated with poor prognosis. In addition, the protein level of TRIM8 is negatively correlated with ER?. RNA sequencing revealed that estrogen signaling maybe a potential target of TRIM8. Moreover, knockdown of TRIM8 can significantly enhance BC cell proliferation and migration both in vitro and in vivo. And this effect can be reversed by ER? depletion. Further mechanistic studies showed that TRIM8 interacts with AF1 domain of ER? via its RING domain in the cytoplasm and increases poly-ubiquitination of the ER? protein. In conclusion, our study reveals an interesting post-translational mechanism between ER? and TRIM8 in ER-positive BC, which suggests that TRIM8 may be a potential therapeutic target in the treatment of BC.

SUBMITTER: Tian Z 

PROVIDER: S-EPMC7642662 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature