Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Elife. 2020 Mar 10;9:e51373. doi: 10.7554/eLife.51373.
The Polycomb-like protein PHF19/PCL3 associates with PRC2 and mediates its recruitment to chromatin in embryonic stem cells. PHF19 is also overexpressed in many cancers. However, neither PHF19 targets nor misregulated pathways involving PHF19 are known. Here, we investigate the role of PHF19 in prostate cancer cells. We find that PHF19 interacts with PRC2 and binds to PRC2 targets on chromatin. PHF19 target genes are involved in proliferation, differentiation, angiogenesis, and extracellular matrix organization. Depletion of PHF19 triggers an increase in MTF2/PCL2 chromatin recruitment, with a genome-wide gain in PRC2 occupancy and H3K27me3 deposition. Transcriptome analysis shows that PHF19 loss promotes deregulation of key genes involved in growth, metastasis, invasion, and of factors that stimulate blood vessels formation. Consistent with this, silencing reduces cell proliferation, while promotes invasive growth and angiogenesis. Our findings reveal a role for PHF19 in controlling the balance between cell proliferation and invasiveness in prostate cancer.
多梳样蛋白 PHF19/PCL3 与 PRC2 相关，并在胚胎干细胞中介导其向染色质的募集。PHF19 在许多癌症中也过表达。然而，PHF19 的靶标或涉及 PHF19 的失调途径都不清楚。在这里，我们研究了 PHF19 在前列腺癌细胞中的作用。我们发现 PHF19 与 PRC2 相互作用，并与染色质上的 PRC2 靶标结合。PHF19 的靶基因参与增殖、分化、血管生成和细胞外基质组织。PHF19 的缺失会触发 MTF2/PCL2 染色质募集的增加，同时全基因组范围内 PRC2 占据和 H3K27me3 沉积增加。转录组分析表明，PHF19 的缺失会促进与生长、转移、侵袭以及刺激血管形成的关键基因的失调。与此一致的是，沉默会降低细胞增殖，同时促进侵袭性生长和血管生成。我们的研究结果揭示了 PHF19 在控制前列腺癌中细胞增殖和侵袭之间平衡的作用。
