Estrogen receptor-[alpha]-miR-1271-SNAI2 feedback loop regulates transforming growth factor-[beta]-induced breast cancer progression

• Published in: Journal of experimental & clinical cancer research Vol. 38; no. 1
• Main Authors: Liu, Bo-Wen, Yu, Zhi-Hao, Chen, Ao-Xiang, Chi, Jiang-Rui, Ge, Jie, Yu, Yue, Cao, Xu-Chen
• Format: Journal Article
• Language: English
• Published: BioMed Central Ltd 01.03.2019
• Subjects: Analysis; Bone morphogenetic proteins; Breast cancer; Chromatin; Development and progression; Estrogens; Fluorescent antibody technique; Hormones; Luciferase; MicroRNA; Phenols (Class of compounds); Progesterone; Sex hormones; Stem cells; Transforming growth factors; Tumors
• ISSN: 0392-9078; 1756-9966
• DOI: 10.1186/s13046-019-1112-4

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-[alpha] (ER[alpha]) or/and progesterone receptor. ER[alpha] 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-[beta] (TGF-[beta]) 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[alpha]-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-[beta]-induced EMT in a miR-1271 dependent manner. Furthermore, ER[alpha] transactivates the miR-1271 expression and is also transcriptionally repressed by SNAI2. Conclusions Our data uncover the ER[alpha]-miR-1271-SNAI2 feedback loop and provide a mechanism to explain the TGF-[beta] network in breast cancer progression. Keywords: Breast cancer, Transforming growth factor-[beta], Epithelial to mesenchymal transition, miR-1271, SNAI2, ER[alpha]