Estrogen receptor-α-miR-1271-SNAI2 feedback loop regulates transforming growth factor-β-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-α (ERα) or/and progesterone receptor. ERα 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-β (TGF-β) 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 ERα-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-β-induced EMT in a miR-1271 dependent manner. Furthermore, ERα transactivates the miR-1271 expression and is also transcriptionally repressed by SNAI2. Conclusions Our data uncover the ERα-miR-1271-SNAI2 feedback loop and provide a mechanism to explain the TGF-β network in breast cancer progression. Electronic supplementary material The online version of this article (10.1186/s13046-019-1112-4) contains supplementary material, which is available to authorized users.

Bile acids increase intestinal markers via FXR/SNAI2/miR-1 axis in the stomach

“…SNAI2 (also known as Slug), a member of Snail superfamily, is one of the transcription factors of epithelial mesenchymal transition (EMT) [32]. In recent years, it has been found that SNAI2 is abnormally expressed in various kinds of malignant tumors and plays an important role in tumor progress and prognosis [33][34][35]. To investigate the role of SNAI2 in IM cells, we examined its expression level in IM tissues and BA-induced IM cells.…”

Interplay among SNAIL Transcription Factor, MicroRNAs, Long Non-Coding RNAs, and Circular RNAs in the Regulation of Tumor Growth and Metastasis

“…Among them are miR-30a [70], miR-122 [95], miR-182 [115], and miR-203 [115] and miR-204 [116]. SLUG is targeted in in oral squamous cell carcinoma by miR-204 [116]; glioblastoma by miR-203 [117]; in lung cancer by miR-1 [118]; in breast cancer by miR-124 [119,120], miR-30a [70], miR-497 [121], miR-1271 [122], and miR-203 [123,124]; in gastric cancer by miR-33a [125]; in lung cancer by miR-218 [126]; in clear cell renal cell carcinoma by miR-1 [127]; in osteosarcoma by miR-124 [128]; and in gingival fibroblasts by miR-200b [129]. Similarly to SNAIL, miRNAs-SLUG action regulates EMT in cancer progression, as well as different processes, such as the modulation of cancer stem cells' activity.…”

“…Cancer/Cell Type References miR-1 lung cancer [118] miR-30a breast cancer [70] miR-33a gastric cancer [125] miR-124 breast cancer [119,120] osteosarcoma [128] glioma [130] miR-200b gingival fibroblasts [129] miR-203 glioblastoma [117] breast cancer [123,124] miR-204 oral squamous cell carcinoma [116] miR-218 lung cancer [126] miR-497 breast cancer [121] miR-630 dermal microvascular endothelial cells [131] miR-1271 breast cancer [122]…”

Perspectives on the Role of Non-Coding RNAs in the Regulation of Expression and Function of the Estrogen Receptor

“…These miRNAs underscore the putative differences between different types of breast cancer [59]. The ERα-miR-1271-SNAI2 axis is involved in the regulation of transforming growth factor (TGF)-β-induced breast cancer progression [60]. miR-301a-3p and miR-129 have been shown to inhibit estrogen signaling through direct interaction with ESR1 and ESR2 genes, respectively [61,62].…”