Targeted Expression of MiR-34a Using the T-VISA System Suppresses Breast Cancer Cell Growth and Invasion

Overview

Journal Mol Ther

Publisher Cell Press

Specialties Molecular Biology
Pharmacology

Date 2012 Oct 4

PMID 23032974

Citations 54

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

Affiliations

Soon will be listed here.

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.

Citing Articles

Shedding Light on the Molecular Diversities of miRNA in Cancer- an Exquisite Mini Review.

Venkatesh S, Manaz P, Priya M, Ambiga G, Basu S Mol Biotechnol. 2024; .

PMID: 39496855 DOI: 10.1007/s12033-024-01312-5.

Dissection of FOXO1-Induced LYPLAL1-DT Impeding Triple-Negative Breast Cancer Progression via Mediating hnRNPK/β-Catenin Complex.

Tang Y, Tian W, Zheng S, Zou Y, Xie J, Zhang J Research (Wash D C). 2023; 6:0289.

PMID: 38111678 PMC: 10726293. DOI: 10.34133/research.0289.

MicroRNAs as Molecular Biomarkers for the Characterization of Basal-like Breast Tumor Subtype.

Tariq M, Richard V, Kerin M Biomedicines. 2023; 11(11).

PMID: 38002007 PMC: 10669494. DOI: 10.3390/biomedicines11113007.

The Implication of microRNAs as non-invasive biomarkers in 179 Egyptian breast cancer female patients.

Shaaban N, Ibrahim N, Saada H, El-Rashidy F, Shaaban H, Elbakary N Oncol Res. 2023; 30(6):269-276.

PMID: 37303494 PMC: 10208075. DOI: 10.32604/or.2022.027277.

Oncolytic viruses: A novel treatment strategy for breast cancer.

Javanbakht M, Tahmasebzadeh S, Cegolon L, Gholami N, Kashaki M, Nikoueinejad H Genes Dis. 2023; 10(2):430-446.

PMID: 37223527 PMC: 10201557. DOI: 10.1016/j.gendis.2021.11.011.

References

Elangovan S, Ramachandran S, Venkatesan N, Ananth S, Gnana-Prakasam J, Martin P . SIRT1 is essential for oncogenic signaling by estrogen/estrogen receptor α in breast cancer. Cancer Res. 2011; 71(21):6654-64. PMC: 3206200. DOI: 10.1158/0008-5472.CAN-11-1446. View

Lin T, Huang X, Gu J, Zhang L, Roth J, Xiong M . Long-term tumor-free survival from treatment with the GFP-TRAIL fusion gene expressed from the hTERT promoter in breast cancer cells. Oncogene. 2002; 21(52):8020-8. DOI: 10.1038/sj.onc.1205926. View

Singletary S, Allred C, Ashley P, Bassett L, Berry D, Bland K . Staging system for breast cancer: revisions for the 6th edition of the AJCC Cancer Staging Manual. Surg Clin North Am. 2003; 83(4):803-19. DOI: 10.1016/S0039-6109(03)00034-3. View

Xie X, Xia W, Li Z, Kuo H, Liu Y, Li Z . Targeted expression of BikDD eradicates pancreatic tumors in noninvasive imaging models. Cancer Cell. 2007; 12(1):52-65. DOI: 10.1016/j.ccr.2007.05.009. View

Cheng J, Zhou L, Xie Q, Xie H, Wei X, Gao F . The impact of miR-34a on protein output in hepatocellular carcinoma HepG2 cells. Proteomics. 2010; 10(8):1557-72. DOI: 10.1002/pmic.200900646. View

Zoller M . CD44: can a cancer-initiating cell profit from an abundantly expressed molecule?. Nat Rev Cancer. 2011; 11(4):254-67. DOI: 10.1038/nrc3023. View

Peurala H, Greco D, Heikkinen T, Kaur S, Bartkova J, Jamshidi M . MiR-34a expression has an effect for lower risk of metastasis and associates with expression patterns predicting clinical outcome in breast cancer. PLoS One. 2011; 6(11):e26122. PMC: 3213093. DOI: 10.1371/journal.pone.0026122. View

Kao J, Salari K, Bocanegra M, Choi Y, Girard L, Gandhi J . Molecular profiling of breast cancer cell lines defines relevant tumor models and provides a resource for cancer gene discovery. PLoS One. 2009; 4(7):e6146. PMC: 2702084. DOI: 10.1371/journal.pone.0006146. View

Zufferey R, Donello J, Trono D, Hope T . Woodchuck hepatitis virus posttranscriptional regulatory element enhances expression of transgenes delivered by retroviral vectors. J Virol. 1999; 73(4):2886-92. PMC: 104046. DOI: 10.1128/JVI.73.4.2886-2892.1999. View

10.

Xie X, Hsu J, Choi M, Xia W, Yamaguchi H, Chen C . A novel hTERT promoter-driven E1A therapeutic for ovarian cancer. Mol Cancer Ther. 2009; 8(8):2375-82. PMC: 2759534. DOI: 10.1158/1535-7163.MCT-09-0056. View

11.

Bartel D . MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136(2):215-33. PMC: 3794896. DOI: 10.1016/j.cell.2009.01.002. View

12.

Lacroix M, Toillon R, Leclercq G . p53 and breast cancer, an update. Endocr Relat Cancer. 2006; 13(2):293-325. DOI: 10.1677/erc.1.01172. View

13.

Lang J, Hsu J, Meric-Bernstam F, Chang C, Wang Q, Bao Y . BikDD eliminates breast cancer initiating cells and synergizes with lapatinib for breast cancer treatment. Cancer Cell. 2011; 20(3):341-56. PMC: 3172580. DOI: 10.1016/j.ccr.2011.07.017. View

14.

Chaffer C, Weinberg R . A perspective on cancer cell metastasis. Science. 2011; 331(6024):1559-64. DOI: 10.1126/science.1203543. View

15.

Garzon R, Marcucci G, Croce C . Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov. 2010; 9(10):775-89. PMC: 3904431. DOI: 10.1038/nrd3179. View

16.

Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H . The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med. 2011; 17(2):211-5. PMC: 3076220. DOI: 10.1038/nm.2284. View

17.

Coombe D, Nakhoul A, Stevenson S, Peroni S, Sanderson C . Expressed luciferase viability assay (ELVA) for the measurement of cell growth and viability. J Immunol Methods. 1998; 215(1-2):145-50. DOI: 10.1016/s0022-1759(98)00081-7. View

18.

Hermeking H . The miR-34 family in cancer and apoptosis. Cell Death Differ. 2009; 17(2):193-9. DOI: 10.1038/cdd.2009.56. View

19.

Templeton N, Lasic D, Frederik P, Strey H, Roberts D, Pavlakis G . Improved DNA: liposome complexes for increased systemic delivery and gene expression. Nat Biotechnol. 1997; 15(7):647-52. DOI: 10.1038/nbt0797-647. View

20.

Gallardo E, Navarro A, Vinolas N, Marrades R, Diaz T, Gel B . miR-34a as a prognostic marker of relapse in surgically resected non-small-cell lung cancer. Carcinogenesis. 2009; 30(11):1903-9. DOI: 10.1093/carcin/bgp219. View