miR-15b-5p Promotes Growth and Metastasis in Breast Cancer by Targeting HPSE2
Balu Wu, Guohong Liu, Yanxia Jin, Tian Yang, Dongdong Zhang, Lu Ding, Fuling Zhou, Yunbao Pan, Yongchang Wei
Abstract
Researchers have been interested in microRNAs (miRNAs) for a long time as they can participate in many biological behaviors of various tumors. Prior studies have reported that miR-15b-5p exhibits a dual effect in prompting or inhibiting tumor progression in different tumors. However, the role of miR-15b-5p in breast cancer (BC) and its functional mechanisms remain unclear. The main objective of this paper is to explore the role and mechanism of miR-15b-5p in BC. This study investigated the role of miR-15b-5p in breast cancer through in vitro and in vivo experiments. Results demonstrated that miR-15b-5p expression was significantly up‐regulated in BC comparison with normal samples and was positively correlated with poor overall survival in patients with BC. Knocking down miR-15b-5p restrained cell growth, invasiveness and induced apoptosis in MCF-7 and MD-MBA-231 cells, while these effects were reversed after overexpression of miR-15b-5p. Next, we revealed a negative correlation between HPSE2 and miR-15b-5p expression in BC tissues and demonstrated that HPSE2 as a direct target of miR-15b-5p via dual-luciferase assay. Knocking down miR-15b-5p significantly increased HPSE2 expression at mRNA and protein levels in BC cells. In addition, miR-15b-5p knockdown significantly inhibited tumorigenicity in BC xenograft model mice. In summary, this study showed that miR-15b-5p promotes breast cancer cells proliferation, migration, and invasion by directly targeting HPSE2 and may serve as a target for the diagnosis and therapy of breast cancer patients.