The microRNA miR-155 is essential for normal immune function;however, persistent up-regulation of miR-155 in B-lymphocytes is associated with cancer development. The broad objectives of this work are to understand how miR-155 over-expression induces tumorigenesis and to assess whether suppressing miR-155 activity can inhibit progression of relevant cancers. The hypotheses of this proposal are: 1) miR-155 promotes cell cycle progression and cell proliferation in B-lymphocytes;2) persistent over-expression of miR-155 in B-lymphocytes thus leads to uncontrolled cell cycle/cell proliferation and ultimately promotes tumorigenesis;and 3) inhibition of miR-155 in tumor cells should restore cell cycle regulation and reverse cancer progression. The following aims shall be addressed to examine these hypotheses.
Aim #1 : Examine whether miR-155 promotes cell cycle progression and cell proliferation in normal B- lymphocytes. MiR-155 will be over-expressed in normal B-lymphocytes. The proliferation rate and the population of these cells in S, M, G1, and G2 cell cycle phases will be compared to control B-lymphocytes. These experiments will address whether over-expression of miR-155 in normal B-lymphocytes is sufficient to disrupt cell cycle and cell proliferation processes.
Aim #2 : Assess the role of cell cycle regulators in mediating miR-155 associated tumorigenesis. A panel of miR-155 targets that regulate cell cycle has been identified;some of these contain putative miR-155 binding sites and have been associated with cancer development. Thus, this aim shall examine whether these genes are directly regulated by miR-155 and whether rescued expression of these genes will inhibit the tumorigenic property of miR-155 in vitro.
Aim #3 : Address whether miR-155 inhibition can restore cell cycle regulation in B-lymphoma cells and reverse tumorigenesis.
This aim shall assess whether suppressing miR-155 activity in cultured B-lymphoma cells will restore normal cell cycle regulation and induce cytotoxicity of these tumor cells. Furthermore, antagomirs that inhibit miR-155 will be injected into mice that have existing lymphomas to examine whether targeting miR-155 could reverse tumor progression.

Public Health Relevance

MiR-155 is associated with various tumors, including leukemias and carcinomas. This study will provide insights of miR-155 function in normal immune responses and how its over-expression induces cancer development. Furthermore, by examining whether inhibiting miR-155 can reverse tumor progression, it may provide a new therapeutic target against relevant cancers.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Postdoctoral Individual National Research Service Award (F32)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-F09-B (20))
Program Officer
Jakowlew, Sonia B
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
California Institute of Technology
Schools of Arts and Sciences
United States
Zip Code
So, Alex Yick-Lun; Sookram, Reeshelle; Chaudhuri, Aadel A et al. (2014) Dual mechanisms by which miR-125b represses IRF4 to induce myeloid and B-cell leukemias. Blood 124:1502-12
So, Alex Yick-Lun; Zhao, Jimmy L; Baltimore, David (2013) The Yin and Yang of microRNAs: leukemia and immunity. Immunol Rev 253:129-45
Chaudhuri, Aadel A; So, Alex Yick-Lun; Mehta, Arnav et al. (2012) Oncomir miR-125b regulates hematopoiesis by targeting the gene Lin28A. Proc Natl Acad Sci U S A 109:4233-8
Raskatov, Jevgenij A; Hargrove, Amanda E; So, Alex Y et al. (2012) Pharmacokinetics of Py-Im polyamides depend on architecture: cyclic versus linear. J Am Chem Soc 134:7995-9
So, Alex Yick-Lun; Garcia-Flores, Yvette; Minisandram, Aarathi et al. (2012) Regulation of APC development, immune response, and autoimmunity by Bach1/HO-1 pathway in mice. Blood 120:2428-37
Chaudhuri, Aadel A; So, Alex Yick-Lun; Sinha, Nikita et al. (2011) MicroRNA-125b potentiates macrophage activation. J Immunol 187:5062-8