PHF19 mediated regulation of proliferation and invasiveness in prostate cancer cells.

ELife
Payal JainLuciano Di Croce

Abstract

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, PHF19 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.

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Citations

Feb 2, 2021·OncoTargets and Therapy·Bolin ChenJiacai Wu
Feb 22, 2021·Cardiovascular Toxicology·Wei GuZhizhong Li
Mar 17, 2021·Nature Reviews. Molecular Cell Biology·Andrea Piunti, Ali Shilatifard
May 18, 2021·Frontiers in Cell and Developmental Biology·Marc García-MontolioLuciano Di Croce
Sep 7, 2021·The Journal of Clinical Endocrinology and Metabolism·Guillermo García-EgurenFelicia A Hanzu

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Datasets Mentioned

BETA
GSE135623

Methods Mentioned

BETA
affinity purification
co-immunoprecipitation
ChIP-seq
ChIPs
immunoprecipitation
ChIP
RNA-seq
ChIP-seqs
transfection
PCR

Software Mentioned

Bowtie
UCSC
GeneOverlap R
MACS
TopHat
Cuffdiff
UCSC genome browser
EnrichR
Cufflinks
DiffBind

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