title: Targeted expression of miR-34a using the T-VISA system suppresses breast cancer cell growth and invasion.
abstract: 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.
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.
authors.forename: Laisheng
authors.initials: L
authors.lastname: Li
authors.forename: Xinhua
authors.initials: X
authors.lastname: Xie
authors.forename: Jinmei
authors.initials: J
authors.lastname: Luo
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Shaoyan
authors.initials: S
authors.lastname: Xi
authors.forename: Jiaoli
authors.initials: J
authors.lastname: Guo
authors.forename: Yanan
authors.initials: Y
authors.lastname: Kong
authors.forename: Minqing
authors.initials: M
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.forename: Zeming
authors.initials: Z
authors.lastname: Xie
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.forename: Weidong
authors.initials: W
authors.lastname: Wei
authors.forename: Mingtian
authors.initials: M
authors.lastname: Yang
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xie
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C522425:MIRN34 microRNA, human; C551848:MIRN34a microRNA, mouse; D035683:MicroRNAs