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@ARTICLE{DAsti:125668,
author = {E. D'Asti and A. Huang and M. Kool$^*$ and B. Meehan and J.
A. Chan and N. Jabado and A. Korshunov$^*$ and S.
Pfister$^*$ and J. Rak},
title = {{T}issue {F}actor {R}egulation by mi{R}-520g in {P}rimitive
{N}euronal {B}rain {T}umor {C}ells: {A} {P}ossible {L}ink
between {O}ncomirs and the {V}ascular {T}umor
{M}icroenvironment.},
journal = {The American journal of pathology},
volume = {186},
number = {2},
issn = {0002-9440},
address = {New York [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2017-01794},
pages = {446 - 459},
year = {2016},
abstract = {Pediatric embryonal brain tumors with multilayered rosettes
demonstrate a unique oncogenic amplification of the
chromosome 19 miRNA cluster, C19MC. Because oncogenic
lesions often cause deregulation of vascular effectors,
including procoagulant tissue factor (TF), this study
explores whether there is a link between C19MC oncogenic
miRNAs (oncomirs) and the coagulant properties of cancer
cells, a question previously not studied. In a pediatric
embryonal brain tumor tissue microarray, we observed an
association between C19MC amplification and reduced fibrin
content and TF expression, indicative of reduced
procoagulant activity. In medulloblastoma cell lines (DAOY
and UW228) engineered to express miR-520g, a biologically
active constituent of the C19MC cluster, we observed reduced
TF expression, procoagulant and TF signaling activities
(responses to factor VIIa stimulation), and diminished TF
emission as cargo of extracellular vesicles. Antimir and
luciferase reporter assays revealed a specific and direct
effect of miR-520g on the TF 3 untranslated region. Although
the endogenous MIR520G locus is methylated in differentiated
cells, exposure of DAOY cells to 5-aza-2-deoxycytidine or
their growth as stem cell-like spheres up-regulated
endogenous miR-520g with a coincident reduction in TF
expression. We propose that the properties of tumors
harboring oncomirs may include unique alterations of the
vascular microenvironment, including deregulation of TF,
with a possible impact on the biology, therapy, and
hemostatic adverse effects of both disease progression and
treatment.},
keywords = {MIRN520 microRNA, human (NLM Chemicals) / MicroRNAs (NLM
Chemicals) / Thromboplastin (NLM Chemicals)},
cin = {G380 / B062},
ddc = {610},
cid = {I:(DE-He78)G380-20160331 / I:(DE-He78)B062-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26687818},
doi = {10.1016/j.ajpath.2015.10.020},
url = {https://inrepo02.dkfz.de/record/125668},
}