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Updated: May 21, 2026
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
Nanoparticle-based therapy in an in vivo microRNA-155 (miR-155)-dependent mouse model of lymphoma
Imran A Babar1, Christopher J Cheng, Carmen J Booth
1Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA.
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.
Insights
Overexpression of microRNA-155 (miR-155) drives lymphoma development. Inhibiting miR-155 with nanoparticles offers a potential therapeutic strategy for pre-B-cell lymphoma and leukemia.
Area of Science:
- Oncology
- Molecular Biology
- Immunoregulation
Background:
- MicroRNA-155 (miR-155) is an oncogenic microRNA implicated in cell division and immune regulation.
- Elevated miR-155 levels are observed in various cancers, often correlating with poor patient prognosis, making it a significant therapeutic target.
Purpose of the Study:
- To investigate the role of miR-155 in lymphoma development and progression.
- To evaluate the efficacy of targeting miR-155 as a therapeutic strategy for miR-155-dependent lymphomas.
Main Methods:
- Induction of miR-155 overexpression in mouse lymphoid tissues to model lymphoma.
- Assessment of tumor regression upon withdrawal of miR-155 expression.
- Systemic administration of antisense peptide nucleic acids encapsulated in polymer nanoparticles to inhibit miR-155 in vivo.
Main Results:
- miR-155 overexpression led to disseminated lymphoma with a clonal pre-B-cell population.
- Cessation of miR-155 expression induced rapid lymphadenopathy regression, attributed to malignant lymphocyte apoptosis.
- Nanoparticle-mediated inhibition of miR-155 effectively slowed the growth of established pre-B-cell tumors in vivo.
Conclusions:
- Lymphoma development is driven by miR-155, establishing tumor dependency on its expression.
- Targeting miR-155 using antisense peptide nucleic acid-loaded nanoparticles presents a promising therapeutic approach for lymphoma and leukemia.
