Molecular mechanism of miR‐153 inhibiting migration, invasion and epithelial‐mesenchymal transition of breast cancer by regulating transforming growth factor beta (TGF‐β) signaling pathway

摘要

Abstract 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.