Targeted Expression of miR-34a Using the T-VISA System Suppresses Breast Cancer Cell Growth and Invasion |
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Authors: | Laisheng Li Xinhua Xie Jinmei Luo Min Liu Shaoyan Xi Jiaoli Guo Yanan Kong Minqing Wu Jie Gao Zeming Xie Jun Tang Xi Wang Weidong Wei Mingtian Yang Mien-Chie Hung Xiaoming Xie |
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Affiliation: | 1. Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People''s Republic of China;2. Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People''s Republic of China;3. Department of Medical Intensive Care Unit, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People''s Republic of China;4. Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, People''s Republic of China;5. State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, People''s Republic of China;6. Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA |
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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. |
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