Nanoparticle-based therapy in an in vivo microRNA-155 (miR-155)-dependent mouse model of lymphoma.
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.
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA.
Imran A
IA
Babar
Christopher J
CJ
Cheng
Carmen J
CJ
Booth
Xianping
X
Liang
Joanne B
JB
Weidhaas
W Mark
WM
Saltzman
Frank J
FJ
Slack
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D004195:Disease Models, Animal; D004318:Doxycycline / Q000494:pharmacology; D005434:Flow Cytometry; D008221:Lymphoid Tissue / Q000378:metabolism; D008223:Lymphoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D053758:Nanoparticles; D016133:Polymerase Chain Reaction
D017931:DNA Primers; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D004318:Doxycycline