Deregulated microRNAs in neurofibromatosis type 1 derived malignant peripheral nerve sheath tumors.

Abstract:

:Malignant peripheral nerve sheath tumors (MPNST) are aggressive cancers that occur spontaneously (sporadic MPNST) or from benign plexiform neurofibromas in neurofibromatosis type 1 (NF1) patients. MPNSTs metastasize easily, are therapy resistant and are frequently fatal. The molecular changes underlying the malignant transformation in the NF1 setting are incompletely understood. Here we investigate the involvement of microRNAs in this process. MicroRNA expression profiles were determined from a series of archival, paired samples of plexiform neurofibroma and MPNST. Ninety differentially expressed microRNAs were identified between the paired samples. Three downregulated microRNAs (let-7b-5p, miR-143-3p, miR-145-5p) and two upregulated microRNAs (miR135b-5p and miR-889-3p) in MPNST were selected for functional characterization. In general, their differential expression was validated in a relevant cell line panel but only partly in a series of unpaired, fresh frozen tumor samples. As part of the validation process we also analyzed microRNA expression profiles of sporadic MPNSTs observing that microRNA expression discriminates NF1-associated and sporadic MPNSTs. The role of microRNAs in cancer progression was examined in NF1-derived MPNST cell lines by transiently modulating microRNA levels. Our findings indicate that some microRNAs affect migratory and invasive capabilities and Wnt signaling activity but the effects are distinct in different cell lines. We conclude that miRNAs play essential regulatory roles in MPNST facilitating tumor progression.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Amirnasr A,Verdijk RM,van Kuijk PF,Kartal P,Vriends ALM,French PJ,van Royen ME,Taal W,Sleijfer S,Wiemer EAC

doi

10.1038/s41598-020-59789-4

subject

Has Abstract

pub_date

2020-02-19 00:00:00

pages

2927

issue

1

issn

2045-2322

pii

10.1038/s41598-020-59789-4

journal_volume

10

pub_type

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