当前位置： SCI文献检索 > NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY期刊下所有文献 > The miR-139-5p regulates proliferation of supratentorial paediatric low-grade gliomas by targeting the PI3K/AKT/mTORC1 signalling.

The miR-139-5p regulates proliferation of supratentorial paediatric low-grade gliomas by targeting the PI3K/AKT/mTORC1 signalling.

Abstract：

AIMS: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. METHODS: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. RESULTS: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. CONCLUSIONS:These findings provide the first evidence that down-regulation of miR-139-5p in supratentorial pLGG drives cell proliferation by derepressing PI3K/AKT signalling.

journal_name

Neuropathol Appl Neurobiol

journal_title

Neuropathology and applied neurobiology

authors

Catanzaro G,Besharat ZM,Miele E,Chiacchiarini M,Po A,Carai A,Marras CE,Antonelli M,Badiali M,Raso A,Mascelli S,Schrimpf D,Stichel D,Tartaglia M,Capper D,von Deimling A,Giangaspero F,Mastronuzzi A,Locatelli F,Ferrett

doi

10.1111/nan.12479

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

687-706

issue

eissn

0305-1846

issn

1365-2990

journal_volume

pub_type

杂志文章

在线工具

The miR-139-5p regulates proliferation of supratentorial paediatric low-grade gliomas by targeting the PI3K/AKT/mTORC1 signalling.