Integrative Genomics Analysis Reveals Silencing of β-Adrenergic Signaling by Polycomb in Prostate Cancer
Copyright policy )Integrative Genomics Analysis Reveals Silencing of β-Adrenergic Signaling by Polycomb in Prostate Cancer
The Polycomb group (PcG) protein EZH2 possesses oncogenic properties for which the underlying mechanism is unclear. We integrated in vitro cell line, in vivo tumor profiling, and genome-wide location data to nominate key targets of EZH2. One of the candidates identified was ADRB2 (Adrenergic Receptor, Beta-2), a critical mediator of beta-adrenergic signaling. EZH2 is recruited to the ADRB2 promoter and represses ADRB2 expression. ADRB2 inhibition confers cell invasion and transforms benign prostate epithelial cells, whereas ADRB2 overexpression counteracts EZH2-mediated oncogenesis. ADRB2 is underexpressed in metastatic prostate cancer, and clinically localized tumors that express lower levels of ADRB2 exhibit a poor prognosis. Taken together, we demonstrate the power of integrating multiple diverse genomic data to decipher targets of disease-related genes.
- National Institute of Health Pakistan
- National Institute of Health United States
- University of Michigan–Flint United States
- National Institutes of Health United States
- National Institute of Health Armenia
Male, Cancer Research, CELLCYCLE, Models, Biological, Mice, Cell Line, Tumor, Animals, Humans, Enhancer of Zeste Homolog 2 Protein, Gene Silencing, Promoter Regions, Genetic, Mice, Inbred BALB C, SYSBIO, Polycomb Repressive Complex 2, Prostatic Neoplasms, Cell Biology, Genomics, DNA-Binding Proteins, Cell Transformation, Neoplastic, Oncology, Receptors, Adrenergic, beta-2, Neoplasm Transplantation, Transcription Factors
Male, Cancer Research, CELLCYCLE, Models, Biological, Mice, Cell Line, Tumor, Animals, Humans, Enhancer of Zeste Homolog 2 Protein, Gene Silencing, Promoter Regions, Genetic, Mice, Inbred BALB C, SYSBIO, Polycomb Repressive Complex 2, Prostatic Neoplasms, Cell Biology, Genomics, DNA-Binding Proteins, Cell Transformation, Neoplastic, Oncology, Receptors, Adrenergic, beta-2, Neoplasm Transplantation, Transcription Factors
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).209 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 1% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!