Recurrence and
metastasis result in a poor prognosis for
breast cancer patients. Recent studies have demonstrated that
microRNAs (
miRNAs) play vital roles in the development and
metastasis of
breast cancer. In this study, we investigated the therapeutic potential of miR-34a in
breast cancer. We found that miR-34a is downregulated in
breast cancer cell lines and tissues, compared with normal cell lines and the adjacent nontumor tissues, respectively. To explore the therapeutic potential of miR-34a, we designed a targeted miR-34a expression plasmid (T-VISA-miR-34a) using the T-VISA system, and evaluated its antitumor effects, efficacy, mechanism of action, and systemic toxicity. T-VISA-miR-34a induced robust, persistent expression of miR-34a, and dramatically suppressed
breast cancer cell growth, migration, and invasion in vitro by downregulating the
protein expression levels of the miR-34a target genes E2F3, CD44, and
SIRT1. In an orthotopic mouse model of
breast cancer,
intravenous injection of T-VISA-miR-34a:liposomal complex nanoparticles significantly inhibited
tumor growth, prolonged survival, and did not induce systemic toxicity. In conclusion, T-VISA-miR-34a lead to robust, specific overexpression of miR-34a in
breast cancer cells and induced potent antitumor effects in vitro and in vivo. T-VISA-miR-34a may provide a potentially useful, specific, and safe-targeted therapeutic approach for
breast cancer.