The Mechanism of the Long Noncoding RNA HOTAIR in Breast Cancer

The long non-coding RNA (lncRNA) HOTAIR has been implicated as a critical regulator of breast cancer metastasis. HOTAIR is frequently overexpressed in breast cancer and is associated with poor prognosis. HOTAIR interacts with a chromatin-modifying complex, Polycomb Repressive Complex 2 (PRC2), to pr...

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Bibliographic Details
Main Author: Meredith, Emily K
Format: Report
Language:English
Subjects:
Anatomy and Physiology
Biochemistry
BIOLOGICAL DETECTION
BREAST CANCER
CELLS(BIOLOGY)
CHROMATIN
CLINICAL MEDICINE
DIAGNOSIS(MEDICINE)
GENE EXPRESSION
GENE SILENCING
HOTAIR REGULATORY NETWORK
IN VITRO ANALYSIS
IN VIVO ANALYSIS
LONG NON-CODING RNAS
MASS SPECTROMETRY
Medicine and Medical Research
METASTASIS
MOLECULAR BIOLOGY
PATHOGENESIS
PROTEINS
RECEPTOR SITES(PHYSIOLOGY)
RIBONUCLEIC ACIDS
TRANSCRIPTION(GENETICS)
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Summary:The long non-coding RNA (lncRNA) HOTAIR has been implicated as a critical regulator of breast cancer metastasis. HOTAIR is frequently overexpressed in breast cancer and is associated with poor prognosis. HOTAIR interacts with a chromatin-modifying complex, Polycomb Repressive Complex 2 (PRC2), to promote the silencing of a subset of genes, including a number of cell-cell adhesion factors. Despite the important role of HOTAIR in cancer progression, the mechanism by which HOTAIR and PRC2 are targeted to specific genomic loci is unknown. Therefore, we have developed a series of biochemical and proteomic approaches to investigate the specificity of HOTAIR targeting in breast cancer cells. We discovered a strikingly specific interaction between the HOTAIR RNA and heterogeneous nuclear ribonucleoprotein (hnRNP) B1. Although B1 is involved in multiple aspects of mRNA processing, our experiments have demonstrated that B1 is also a critical component of the HOTAR-induced gene silencing machinery. Through a combination of in vitro and in vivo approaches, we have determined that B1 can engage HOTAIR on chromatin, and can modulate HOTAIR-induced silencing marks. By identifying key interaction partners of HOTAIR, we will define the mechanism of HOTAIR- induced gene silencing and reveal how aberrant expression of this lncRNA promotes breast cancer metastasis. The original document contains color images.