MicroRNA‑133b targets TGFβ receptor I to inhibit TGF‑β‑induced epithelial‑to‑mesenchymal transition and metastasis by suppressing the TGF‑β/SMAD pathway in breast cancer

Abstract

Breast cancer (BC) is one of the most common types of cancer and the leading cause of cancer-associated mortality among women worldwide. Accumulating evidence indicates that microRNA (miR)-133b inhibits the proliferation and invasion of cancer cells. Considering that transforming growth factor (TGF)-β signaling plays a key role in cellular epithelial-to-mesenchymal transition (EMT) and cancer metastasis, it is crucial to explore the roles and underlying molecular mechanisms of miR-133b in regulating TGF-β-induced EMT during progression of BC. In the present study, an inverse correlation was observed between the expression of miR-133b and TGFβ receptor I (TGFβR1) mRNA in BC cells and tissues. Furthermore, miR-133b expression was found to be decreased in the BC tissues of patients with lymph node metastasis and advanced tumor-node-metastasis stage, while the expression of TGFβR1 was upregulated. Overexpression of miR‑133b significantly decreased the expression of TGFβR1, an indispensable receptor of TGF-β/SMAD signaling, and suppressed TGF-β-induced EMT and BC cell invasion in vitro, whereas miR-133b knockdown exerted the opposite effects. Mechanistically, TGFβR1 was verified as a direct target of miR-133b as determined by bioinformatics analysis and a dual-luciferase reporter assay. In addition, small interfering RNA-mediated knockdown of TGFβR1 mimicked the phenotype of miR-133b overexpression in BC cells. Furthermore, miR-133b overexpression suppressed BC cell invasion in vivo. Collectively, the findings of the present study indicated that miR-133bactsasatumorsuppressor,inhibitingTGF-β-induced EMT and metastasis by directly targeting TGFβR1, and suppressing the TGF-β/SMAD pathway. Therefore, miR-133b may be of value as a diagnostic biomarker of BC.