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@ARTICLE{Catanzaro:141996,
author = {G. Catanzaro and Z. M. Besharat and E. Miele and M.
Chiacchiarini and A. Po and A. Carai and C. E. Marras and M.
Antonelli and M. Badiali and A. Raso and S. Mascelli and D.
Schrimpf$^*$ and D. Stichel$^*$ and M. Tartaglia and D.
Capper$^*$ and A. von Deimling$^*$ and F. Giangaspero and A.
Mastronuzzi and F. Locatelli and E. Ferretti},
title = {{T}he mi{R}-139-5p regulates proliferation of
supratentorial paediatric low-grade gliomas by targeting the
{PI}3{K}/{AKT}/m{TORC}1 signalling.},
journal = {Neuropathology $\&$ applied neurobiology},
volume = {44},
number = {7},
issn = {0305-1846},
address = {Oxford [u.a.]},
publisher = {Wiley-Blackwell},
reportid = {DKFZ-2018-02226},
pages = {687 - 706},
year = {2018},
abstract = {Paediatric low-grade gliomas (pLGGs) are a heterogeneous
group of brain tumours associated with a high overall
survival: however, they are prone to recur and
supratentorial lesions are difficult to resect, being
associated with high percentage of disease recurrence. Our
aim was to shed light on the biology of pLGGs.We performed
microRNA profiling on 45 fresh-frozen grade I tumour samples
of various histological classes, resected from patients aged
≤16 years. We identified 93 microRNAs specifically
dysregulated in tumours as compared to non-neoplastic brain
tissue. Pathway analysis of the microRNAs signature revealed
PI3K/AKT signalling as one of the centrally enriched
oncogenic signalling. To date, activation of the PI3K/AKT
pathway in pLGGs has been reported, although activation
mechanisms have not been fully investigated yet.One of the
most markedly down-regulated microRNAs in our supratentorial
pLGGs cohort was miR-139-5p, whose targets include the gene
encoding the PI3K's (phosphatidylinositol 3-kinase)
catalytic unit, PIK3CA. We investigated the role of
miR-139-5p in regulating PI3K/AKT signalling by the use of
human cell cultures derived from supratentorial pLGGs.
MiR-139-5p overexpression inhibited pLGG cell proliferation
and decreased the phosphorylation of PI3K target AKT and
phosphorylated-p70 S6 kinase (p-p70 S6K), a hallmark of
PI3K/AKT/mTORC1 signalling activation. The effect of
miR-139-5p was mediated by PI3K inhibition, as suggested by
the decrease in proliferation and phosphorylation of AKT and
p70 S6K after treatment with the direct PI3K inhibitor
LY294002.These findings provide the first evidence that
down-regulation of miR-139-5p in supratentorial pLGG drives
cell proliferation by derepressing PI3K/AKT signalling.},
cin = {L201 / G380},
ddc = {610},
cid = {I:(DE-He78)L201-20160331 / I:(DE-He78)G380-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29478280},
doi = {10.1111/nan.12479},
url = {https://inrepo02.dkfz.de/record/141996},
}