The Status of EGFR Modulates the Effect of miRNA-200c on ZEB1 Expression and Cell Migration in Glioblastoma Cells.

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Autores de INCLIVA

Participantes ajenos a INCLIVA

  • Calabuig-Farinas, Silvia

Grupos y Plataformas de I+D+i

Abstract

Migration of glioblastoma cells into surrounding tissue is one of the main features that makes this tumor incurable. We evaluated whole-genome miRNA expression profiling associated with different EGFR amplification patterns in 30 cases of primary glioblastoma. From the 64 miRNAs that showed differential expression between tumors with a high level of EGFR amplification and tumors without EGFR amplification, 40% were related with cell migration, being miR-200c the most differentially expressed between these two groups. We investigated the effect of miR-200c on ZEB1 expression and cell migration in an in vitro transfection model with a miR-200c mimic, a miR-200c inhibitor and siRNA targeting EGFR in three short-term cultures with different levels of EGFR amplification obtained from resected glioblastomas. The cell culture with the highest EGFR amplification level presented the lowest miR-200c expression and the status of EGFR modulated the effect of miR-200c on ZEB1 expression. Silencing EGFR led to miR-200c upregulation and ZEB1 downregulation in transfected cultures, except in the presence of high levels of EGFR. Likewise, miR-200c upregulation decreased ZEB1 expression and inhibited cell migration, especially when EGFR was not amplified. Our results suggest that modulating miR-200c may serve as a novel therapeutic approach for glioblastoma depending on EGFR status.

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)

Datos de la publicación

ISSN/ISSNe:
1661-6596, 1422-0067

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES  MDPI AG

Tipo:
Article
Páginas:
-
PubMed:
33396457

Citas Recibidas en Web of Science: 11

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Keywords

  • glioblastoma; EGFR amplification; miR-200c; ZEB1; cell migration

Campos de Estudio

Financiación

Proyectos y Estudios Clínicos

Interacción de miRNA-200 y miRNA-138 en la infiltración y perfiles de MMI biomarcadores en el diagnostico, pronostico y terapéutico.

Investigador Principal: MIGUEL CERDA NICOLAS

PI14/01669 . INSTITUTO SALUD CARLOS III . 2015

ESTUDIO METABOLOMICO DE LA INTERACCIÓN HUESPED-MICROBIOTA INTESTINAL EN LA ENFERMEDAD CARDIOMETABÓLICA. DETECCIÓN TEMPRANA, PREVENCION Y TRATAMIENTO.

Investigador Principal: DANIEL MONLEON SALVADO

SAF2014-52875-R . MINISTERIO ECONOMIA Y COMPETITIVIDAD . 2015

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