Epigenetic aberrations are a key driver of cancer pathogenesis. Long intergenic noncoding RNAs (lincRNAs) have emerged as a pervasive and important class of regulators that serve as the interface between DNA and chromatin modification machinery. The lincRNA HOTAIR is overexpressed in approximately a third of human breast carcinomas and is a powerful predictor of eventual metastasis and death. HOTAIR reprograms the breast cancer chromatin state to alter the positional identity of the cancer cells, enabling invasion and metastatic spread to distant organs. The long term goal of this project is to understand the mechanistic basis of lincRNA action in human cancers. First, using HOTAIR as a model system, we will address the structure-function relationship of a lincRNA and its oncogenic activities. Second, we will examine how HOTAIR targets specific genomic loci to relocalize Polycomb proteins. Third, we will determine whether HOTAIR may serve as a therapeutic target by testing its ongoing requirement during cancer progression. These experiments will provide key insights into how long noncoding RNAs may instigate cancer progression, and should pave the way for new cancer diagnostics and treatments in the future. !

Public Health Relevance

Breast cancer is the second most common cause of cancer death for women in the United States. These deaths are most often caused by the spread of breast cancer to other sites of the body. A new type of genes, termed long intergenic noncoding RNA (lincRNA) has been found to be important to promote breast cancer progression by increasing metastasis. Research into how lincRNAs change gene activities in breast cancer will help to improve the risk assessment of breast cancer patients and identify targets for cancer therapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA118750-08
Application #
8676685
Study Section
Tumor Progression and Metastasis Study Section (TPM)
Program Officer
Jhappan, Chamelli
Project Start
2005-12-01
Project End
2017-05-31
Budget Start
2014-06-02
Budget End
2015-05-31
Support Year
8
Fiscal Year
2014
Total Cost
$288,234
Indirect Cost
$109,463
Name
Stanford University
Department
Dermatology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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Tsai, Miao-Chih; Spitale, Robert C; Chang, Howard Y (2011) Long intergenic noncoding RNAs: new links in cancer progression. Cancer Res 71:3-7

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