Abstract |
Pediatric low-grade gliomas (pLGGs) are a heterogeneous group of grade I and II glial tumors,
whose mainstay of treatment is surgical resection. A subset of patients present tumor progression
requiring adjuvant chemotherapy and/or radiotherapy, that often carry unsatisfactory results and
long-term morbidity.
Several studies have focused and clarified the genomic aspects of pLGGs. To date, activation of the
PI3K/AKT pathway in pLGGs has been reported, although activation mechanisms have not been
fully investigated yet. Initially, we performed experiments based on previously published data that
demonstrate the role of miR-139-5p in regulating PI3K/AKT signaling in 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
signaling activation.
Despite the progress in pLGG molecular characterization, up to date no biomarker predicting
clinical outcome is available. For this purpose, microRNA profiles of 104 pLGG samples were
collected from four European pediatric neuro-oncology centers and their microRNA profiles were
analyzed.
Low expression of miR-376a-3p and miR-888-5p was associated with tumor progression and poor
overall survival. Expression levels of these microRNAs, according to enrichment analyses, were
linked to tumor growth and cancer invasion pathways.
These microRNAs might represent prognostic biomarkers able to stratify pLGG patients at the time
of diagnosis. Additionally, the molecular aspects of these microRNAs could be significant for the
identification of new target therapies.
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