Objective: To investigate the role and mechanism of action of miR-153 in the migration, invasion, and epithelial-mesenchymal transition (EMT) of breast cancer cells. Methods: Quantitative real time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-153 and transforming growth factor beta receptor 2 (TGFBR2) in tissue specimens and cells. miR-153 overexpression in breast cancer cells was achieved by miR-153 mimic transfection. Mobility and invasiveness of breast cancer cells were evaluated by transwell assay. EMT was evaluated by Western blot detecting the protein level of E-cadherin and Vimentin. Interaction of miR-153 and 3′-untranslated region (UTR) of TGFBR2 messenger RNA (mRNA) was investigated by luciferase reporter assay. Results: The expression of miR-153 in breast cancer tissue specimens and MDA-MB-231 cells was significantly lower than that in nonmalignant counterparts, inversely correlating with that of TGFBR2 mRNA. Transfection with miR-153 mimic significantly increased miR-153 level in MDA-MB-231 cells while inhibiting its migration, invasion, and EMT in vitro, which could be mimicked by TGFBR2 knockdown. Luciferase reporter assay confirmed two targets of miR-153 on the 3′-UTR of TGFBR2 mRNA. Restoring TGFBR2 protein level by transient overexpression largely rescued migration, invasion, and EMT of MDA-MB-231 cells that were repressed by miR-153 mimic transfection.Conclusion: miR-153 inhibits breast cancer cell migration, invasion, and EMT by targeting TGFBR2. K E Y W O R D S epithelial-mesenchymal transition (EMT), invasion, migration, miR-153, transforming growth factor beta receptor 2 (TGFBR2) | INTRODUCTIONBreast cancer is one of the most common malignant tumors and the main cause of cancer-related death in women. Breast cancer cell invasion and metastasis have been proposed as the major cause of therapeutic failure. 1 Therefore, exploring the molecular mechanism of invasion and metastasis of breast cancer cells might J Cell Biochem. 2019;120:9539-9546.wileyonlinelibrary.com/journal/jcb