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@ARTICLE{Pickl:130330,
author = {J. M. A. Pickl$^*$ and D. Tichy$^*$ and V. Kuryshev$^*$ and
Y. Tolstov and M. Falkenstein and J. Schüler and D.
Reidenbach$^*$ and A. Hotz-Wagenblatt$^*$ and G. Kristiansen
and W. Roth and B. Hadaschik and M. Hohenfellner and S.
Duensing and D. Heckmann$^*$ and H. Sültmann$^*$},
title = {{A}go-{RIP}-{S}eq identifies {P}olycomb repressive complex
{I} member {CBX}7 as a major target of mi{R}-375 in prostate
cancer progression.},
journal = {OncoTarget},
volume = {7},
number = {37},
issn = {1949-2553},
address = {[S.l.]},
publisher = {Impact Journals LLC},
reportid = {DKFZ-2017-05409},
pages = {59589 - 59603},
year = {2016},
abstract = {Prostate cancer is a heterogeneous disease. MiR-375 is a
marker for prostate cancer progression, but its cellular
function is not characterized. Here, we provide the first
comprehensive investigation of miR-375 in prostate cancer.
We show that miR-375 is enriched in prostate cancer compared
to normal cells. Furthermore, miR-375 enhanced
proliferation, migration and invasion in vitro and induced
tumor growth and reduced survival in vivo showing that
miR-375 has oncogenic properties in prostate cancer. On the
molecular level, we provide the targetome and genome-wide
transcriptional changes of miR-375 expression by applying a
generalized linear model for Ago-RIP-Seq and RNA-Seq, and
show that miR-375 is involved in tumorigenic networks and
Polycomb regulation. Integration of tissue and gene ontology
data prioritized miR-375 targets and identified the tumor
suppressor gene CBX7, a member of Polycomb repressive
complex 1, as a major miR-375 target. MiR-375-mediated
repression of CBX7 was accompanied by increased expression
of its homolog CBX8 and activated transcriptional programs
linked to malignant progression in prostate cancer cells.
Tissue analysis showed association of CBX7 loss with
advanced prostate cancer. Our study indicates that miR-375
exerts its tumor-promoting role in prostate cancer by
influencing the epigenetic regulation of transcriptional
programs through its ability to directly target the Polycomb
complex member CBX7.},
cin = {B063 / C060 / W180 / L101},
ddc = {610},
cid = {I:(DE-He78)B063-20160331 / I:(DE-He78)C060-20160331 /
I:(DE-He78)W180-20160331 / I:(DE-He78)L101-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27449098},
pmc = {pmc:PMC5312160},
doi = {10.18632/oncotarget.10729},
url = {https://inrepo02.dkfz.de/record/130330},
}