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.

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‑133b acts as a tumor suppressor, inhibiting TGF‑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.