Human B-cell lymphoma is a significant clinical problem that is rising in incidence and prevalence as the American population ages. At the molecular level, changes in gene expression are central to both oncogenesis and developmental processes. Recently it has come to light that non-coding RNAs are central players in regulating gene expression. Extending our prior work in microRNAs, we now propose to analyze the contribution of a long non-coding RNA, Malat-1 to B-cell development and oncogenesis. Our preliminary data shows that Malat-1 is differentially regulated during the activation of B-cells, and recent publications implicate it as a target of activation-induced deaminase (AID), which can induce oncogenic translocations in germinal center B-cells. We therefore hypothesize that Malat1 may influence B-cell development and oncogenesis. Here, we propose to study the expression pattern of Malat1 in B-cell differentiation, and to understand its oncogenic function via gain and loss-of-function approaches in murine B-cells. These studies will delve into a novel, poorly understood field, as virtually nothing is known about long non-coding RNAs in B-cell lymphoma. In completing these aims, we will generate the necessary preliminary data to apply for a R01 grant. The completion of these goals promises to significantly increase our understanding of critical biological and pathological processes.

Public Health Relevance

B-cell non-Hodgkin lymphoma is a significant health problem in the United States and its incidence has increased dramatically in the past 30 years. This proposal seeks to bring together remarkable progress in non-coding RNA research with this important disease to solve problems in pathogenesis. Successful completion of this proposal will lead to new approaches to lymphoma diagnosis, classification and therapy, and will improve the lives of countless Americans who suffer from B-cell non-Hodgkin lymphoma.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
1R03CA175426-01A1
Application #
8638750
Study Section
Special Emphasis Panel (ZCA1-RTRB-Z (O1))
Program Officer
Duglas-Tabor, Yvonne
Project Start
2014-01-01
Project End
2015-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
1
Fiscal Year
2014
Total Cost
$77,000
Indirect Cost
$27,000
Name
University of California Los Angeles
Department
Pathology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095