Nanoparticle-based therapy in an in vivo microRNA-155 (miR-155)-dependent mouse model of lymphoma

IA Babar, CJ Cheng, CJ Booth… - Proceedings of the …, 2012 - National Acad Sciences
IA Babar, CJ Cheng, CJ Booth, X Liang, JB Weidhaas, WM Saltzman, FJ Slack
Proceedings of the National Academy of Sciences, 2012National Acad Sciences
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 …
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.
National Acad Sciences