MicroRNA-615-5p regulates the proliferation and apoptosis of breast cancer cells by targeting HSF1.

Abstract

Breast cancer, which commonly occurs in the epithelium of the mammary gland, is a malignant tumor. MicroRNAs are involved in various cancer-associated processes, and microRNA-615-5p has been identified to be decreased in the pathological tissues from patients with breast cancer. In the present study, the possible mechanism of microRNA-615-5p in the progression of breast cancer was investigated in order to identify potential novel targets for clinical treatment. Heat shock factor 1 (HSF1) was identified as a predictive target gene of microRNA-615-5p using TargetScan analysis. The expression levels of microRNA-615-5p and its target gene, HSF1, were measured in breast cancer tissues and normal adjacent tissues. Additionally, the effects of microRNA-615-5p on MCF-7 breast cancer cell growth and apoptosis were examined. Furthermore, the interaction between HSF1 and microRNA-615-5p was investigated by a dual luciferase gene reporter assay. The expression levels of HSF1 were measured following transfection with microRNA-615-5p or pcDNA3.1-HSF1. Finally, the expression levels of proliferation- and apoptosis-associated factors such as B-cell lymphoma 2 (Bcl-2), cyclin D1, proliferating cell nuclear antigen (PCNA) and bcl-2-like protein 4 (Bax) were determined. The results demonstrated that lower microRNA-615-5p expression and higher HSF1 mRNA expression were present in tumor tissues compared with adjacent tissues (P<0.01). HSF1 was verified as a direct target of microRNA-615-5p using the dual luciferase gene reporter assay. In comparison with untransfected control and mimic-transfected negative control (NC) cells, MCF-7 cells transfected with microRNA-615-5p mimics exhibited reduced cell proliferation and increased apoptosis (P<0.01). However, the overexpression of HSF1 using a vector reversed the suppression of HSF1 induced by microRNA-615-5p mimics (P<0.01). The mRNA and protein expression levels of Bax were significantly increased, whereas those of Bcl-2, cyclin D1 and PCNA were decreased in the cells transfected with microRNA-615-5p mimics compared with the control and NC cells (P<0.01). Collectively, the present study indicated that microRNA-615-5p may mediate the progression of breast cancer by targeting HSF1.