• Home
  1. Home
  2. Human tissue engineering allows the identification of active miRNA regulators of glioblastoma aggressiveness
Scientific article
English

Human tissue engineering allows the identification of active miRNA regulators of glioblastoma aggressiveness

Contributors

Cosset, Erika; Petty Ii, Thomas John; Dutoit Vallotton, Valérie; Tirefort, Diderik; Otten-Hernandez, P; Farinelli, Laurent Luca Denis; Dietrich, Pierre-Yves; Preynat-Seauve, Olivier

Published in

Biomaterials, vol. 107, p. 74-87

Publication date

2016

Abstract

Glioblastoma multiforme (GBM) is among the most aggressive cancers associated with massive infiltration of peritumoral parenchyma by migrating tumor cells. The infiltrative nature of GBM cells, the intratumoral heterogeneity concomitant with redundant signaling pathways likely underlie the inability of conventional and targeted therapies to achieve long-term remissions. In this respect, microRNAs (miRNAs), which are endogenous small non-coding RNAs that play a role in cancer aggressiveness, emerge as possible relevant prognostic biomarkers or therapeutic targets for treatment of malignant gliomas. We previously described a tissue model of GBM developing into a stem cell-derived human Engineered Neural Tissue (ENT) that allows the study of tumor/host tissue interaction. Combined with high throughput sequencing analysis, we took advantage of this human and integrated tissue model to understand miRNAs regulation. Three miRNAs (miR-340, -494 and -1293) active on cell proliferation, adhesion to extracellular matrix and tumor cell invasion were identified in GBM cells developing within ENT, and also confirmed in GBM biopsies. The components of miRNAs regulatory network at the transcriptional and the protein level have been also revealed by whole transcriptome analysis and Tandem Mass Tag in transfected GBM cells. Notably, miR-340 has a clinical relevance and modulates the expression of miR-494 and -1293, emphasizing its biological significance. Altogether, these findings demonstrate that human tissue engineering modeling GBM development in neural host tissue is a suitable tool to identify active miRNAs. Collectively, our study identified miR-340 as a strong modulator of GBM aggressiveness which may constitute a therapeutic target for treatment of malignant gliomas.

UNIGE affiliation entities

UNIGE research groups

Citation (ISO format)

COSSET, Erika et al. Human tissue engineering allows the identification of active miRNA regulators of glioblastoma aggressiveness. In: Biomaterials, 2016, vol. 107, p. 74–87. doi: 10.1016/j.biomaterials.2016.08.009

Main files (1)

Article (Published version)

Identifiers

Journal ISSN

0142-9612
577views
5downloads

Technical informations

Creation

26/09/2017 12:29:00

First validation

26/09/2017 12:29:00

Update

15/03/2023 02:03:41

Status update

15/03/2023 02:03:41

Last indexation

31/10/2024 07:53:10
All rights reserved by Archive ouverte UNIGE and the University of Geneva
OpenAIRE Indexed & Validated