MicroRNA-153 inhibits cell proliferation, migration, invasion and epithelial-mesenchymal transition in breast cancer via direct targeting of RUNX2.

Abstract

A number of microRNAs (miRNAs) are involved in the development and malignant progression of numerous types of human cancer including breast cancer. The underlying regulatory mechanism of miRNA-153 (miR-153) in breast cancer progression remains largely unknown. The present study demonstrated that miR-153 expression levels were significantly reduced in breast cancer tissue samples and cell lines, compared with adjacent healthy tissue samples and normal human breast cell line MCF-10A. In addition, low miR-153 expression was associated with advanced clinical staging and metastasis in patients with breast cancer. However, no association with age, subtype or differentiation was identified. Furthermore, patients with breast cancer with low miR-153 expression had poor prognosis, compared with patients with breast cancer with high miR-153 expression. Overexpression of miR-153 reduced proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in breast cancer SK-BR-3 and BT-549 cells. Runt-related transcription factor 2 (RUNX2), which was revealed to be significantly upregulated in breast cancer, was verified as a target gene of miR-153 in SK-BR-3 and BT-549 cells by luciferase reporter gene assay. High RUNX2 expression was associated with advanced clinical staging as well as distant and lymph node metastasis in patients with breast cancer. However, no association with age, subtype or differentiation was identified. Additionally, an inverse correlation between miR-153 and RUNX2 mRNA expression levels was observed in breast cancer tissues. RUNX2 overexpression reduced the suppressive effects of miR-153 on the proliferation, migration, invasion and EMT of SK-BR-3 and BT-549 cells. The present study indicated that miR-153 may serve a role in breast tumor growth and metastasis via direct targeting of RUNX2. The miR-153/RUNX2 axis may be used as a potential therapeutic target in breast cancer treatment.