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Free keywords:
Adenocarcinoma/*genetics/metabolism/pathology
Biomarkers, Tumor/genetics
Cell Division
Cell Line, Tumor
Chromosomal Proteins, Non-Histone/biosynthesis/genetics/*physiology
CpG Islands
DNA Methylation
*Epigenetic Repression
Follow-Up Studies
*Gene Expression Regulation, Neoplastic
Humans
Male
Neoplasm Invasiveness/genetics
Neoplasm Metastasis/*genetics
Neoplasm Proteins/biosynthesis/genetics/*physiology
Polycomb Repressive Complex 2/physiology
Prognosis
Prostatic Neoplasms/*genetics/metabolism/pathology
Protein Interaction Mapping
RNA, Neoplasm/biosynthesis
RNA, Ribosomal/biosynthesis
Up-Regulation
Abstract:
Prostate cancer is driven by a combination of genetic and/or epigenetic alterations. Epigenetic alterations are frequently observed in all human cancers, yet how aberrant epigenetic signatures are established is poorly understood. Here we show that the gene encoding BAZ2A (TIP5), a factor previously implicated in epigenetic rRNA gene silencing, is overexpressed in prostate cancer and is paradoxically involved in maintaining prostate cancer cell growth, a feature specific to cancer cells. BAZ2A regulates numerous protein-coding genes and directly interacts with EZH2 to maintain epigenetic silencing at genes repressed in metastasis. BAZ2A overexpression is tightly associated with a molecular subtype displaying a CpG island methylator phenotype (CIMP). Finally, high BAZ2A levels serve as an independent predictor of biochemical recurrence in a cohort of 7,682 individuals with prostate cancer. This work identifies a new aberrant role for the epigenetic regulator BAZ2A, which can also serve as a useful marker for metastatic potential in prostate cancer.
