Estrogen receptor-?-miR-1271-SNAI2 feedback loop regulates transforming growth factor-?-induced breast cancer progression.

ABSTRACT: BACKGROUND:Breast cancer is the most common cancer among women worldwide, and approximately 70% of breast cancers are hormone receptor-positive and express estrogen receptor-? (ER?) or/and progesterone receptor. ER? has been identified to promote the growth of primary breast cancer, however, it can also antagonize signaling pathways that lead to epithelial-mesenchymal transition (EMT), including transforming growth factor-? (TGF-?) signaling. miRNA alteration or dysfunction is involved in cancer development and progression. Although miR-1271 has identified as a tumor suppressor in various cancers, the role of miR-1271 in breast cancer is still limited. METHODS:The effect of miR-1271 on breast cancer progression was investigated both in vitro and in vivo. The EMT-related protein expression levels and localization were analyzed by western blotting and immunofluorescence, respectively. Chromatin immunoprecipitation and dual-luciferase reporter assays were used to validate the regulation of ER?-miR-1271-SNAI2 feedback loop. RESULTS:miR-1271 suppresses breast cancer progression and EMT phenotype both in vitro and in vivo by targeting SNAI2. Estrogen reverses TGF-?-induced EMT in a miR-1271 dependent manner. Furthermore, ER? transactivates the miR-1271 expression and is also transcriptionally repressed by SNAI2. CONCLUSIONS:Our data uncover the ER?-miR-1271-SNAI2 feedback loop and provide a mechanism to explain the TGF-? network in breast cancer progression.

SUBMITTER: Liu BW 

PROVIDER: S-EPMC6397493 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature