Nanoparticle-based therapy in an in vivo microRNA-155 (miR-155)-dependent mouse model of lymphoma
- 8 June 2012
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 109 (26), E1695-704
- https://doi.org/10.1073/pnas.1201516109
Abstract
MicroRNA-155 (miR-155) is an oncogenic microRNA that regulates several pathways involved in cell division and immunoregulation. It is overexpressed in numerous cancers, is often correlated with poor prognosis, and is thus a key target for future therapies. In this work we show that overexpression of miR-155 in lymphoid tissues results in disseminated lymphoma characterized by a clonal, transplantable pre-B-cell population of neoplastic lymphocytes. Withdrawal of miR-155 in mice with established disease results in rapid regression of lymphadenopathy, in part because of apoptosis of the malignant lymphocytes, demonstrating that these tumors are dependent on miR-155 expression. We show that systemic delivery of antisense peptide nucleic acids encapsulated in unique polymer nanoparticles inhibits miR-155 and slows the growth of these "addicted" pre-B-cell tumors in vivo, suggesting a promising therapeutic option for lymphoma/leukemia.Keywords
This publication has 70 references indexed in Scilit:
- Enhanced siRNA delivery into cells by exploiting the synergy between targeting ligands and cell-penetrating peptidesBiomaterials, 2011
- Nanoparticles Deliver Triplex-forming PNAs for Site-specific Genomic Recombination in CD34+ Human Hematopoietic ProgenitorsMolecular Therapy, 2011
- Origin of Chromosomal Translocations in Lymphoid CancerCell, 2010
- Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor modelNature Biotechnology, 2010
- Onco‐miR‐155 targets SHIP1 to promote TNFα‐dependent growth of B cell lymphomasEMBO Molecular Medicine, 2009
- miR-155 gene: A typical multifunctional microRNABiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2009
- Reversal of HIV-1 latency with anti-microRNA inhibitorsThe International Journal of Biochemistry & Cell Biology, 2008
- Silencing of microRNAs in vivo with ‘antagomirs’Nature, 2005
- BIC and miR‐155 are highly expressed in Hodgkin, primary mediastinal and diffuse large B cell lymphomasThe Journal of Pathology, 2005
- The Hallmarks of CancerCell, 2000