Reference SummaryBabar IA, Proc Natl Acad Sci U S A 2012 Jun 26;109(26):E1695-704

Title

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

Authors

Babar IA; Cheng CJ; Booth CJ; Liang X; Weidhaas JB; Saltzman WM; Slack FJ

Journal

Proc Natl Acad Sci U S A

Volume

109

Issue

26

Year

2012

Pages

E1695-704

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.

Links

J:185598 – MGI References
22685206 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
B6;FVB-Gt(ROSA)26Sortm1(tTA,tetO-Mir155)Fjsl/Gt(ROSA)26Sor Tg(Nes-cre)1Wmz CNS - Brain tumor
  • doxycycline
CNS - Brain

0

B6;FVB-Gt(ROSA)26Sortm1(tTA,tetO-Mir155)Fjsl/Gt(ROSA)26Sor CNS - Brain tumor
  • Adenovirus carrying cre recombinase
  • doxycycline
CNS - Brain

0

B6;FVB-Gt(ROSA)26Sortm1(tTA,tetO-Mir155)Fjsl/Gt(ROSA)26Sor Tg(Nes-cre)1Wmz Leukocyte - Lymphocyte - B-lymphocyte lymphoma
  • doxycycline
Leukocyte - Lymphocyte - B-lymphocyte

observed

B6;FVB Leukocyte - Lymphocyte - B-lymphocyte lymphoma
  • doxycycline
Leukocyte - Lymphocyte - B-lymphocyte

0

B6;FVB-Gt(ROSA)26Sortm1(tTA,tetO-Mir155)Fjsl/Gt(ROSA)26Sor Tg(Nes-cre)1Wmz Liver hyperplasia
  • doxycycline
Liver

observed

B6;FVB-Gt(ROSA)26Sortm1(tTA,tetO-Mir155)Fjsl/Gt(ROSA)26Sor Tg(Nes-cre)1Wmz Lymph node hyperplasia
  • doxycycline
Lymph node

0 - observed

B6;FVB Lymph node hyperplasia Lymph node

0

B6;FVB-Gt(ROSA)26Sortm1(tTA,tetO-Mir155)Fjsl/Gt(ROSA)26Sor Tg(Nes-cre)1Wmz Spleen hyperplasia
  • doxycycline
Spleen

0 - observed

B6;FVB Spleen hyperplasia Spleen

0

B6;FVB-Gt(ROSA)26Sortm1(tTA,tetO-Mir155)Fjsl/Gt(ROSA)26Sor Tg(Nes-cre)1Wmz Thymus hyperplasia
  • doxycycline
Thymus

observed

B6;FVB Thymus hyperplasia Thymus

0