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GATA-4, a potential novel therapeutic target for high-grade meningioma, regulates miR-497, a potential novel circulating biomarker for high-grade meningioma

BACKGROUND: Meningiomas are the most common primary intracranial tumours. They are classified as grade I, II, and III based on their histopathological features. While most meningiomas can be managed by surgery alone, adjuvant treatment may be required in case of recurrent, or high-grade tumours. To...

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Autores principales: Negroni, Caterina, Hilton, David A., Ercolano, Emanuela, Adams, Claire L., Kurian, Kathreena M., Baiz, Daniele, Hanemann, C.Oliver
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452696/
https://www.ncbi.nlm.nih.gov/pubmed/32810829
http://dx.doi.org/10.1016/j.ebiom.2020.102941
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author Negroni, Caterina
Hilton, David A.
Ercolano, Emanuela
Adams, Claire L.
Kurian, Kathreena M.
Baiz, Daniele
Hanemann, C.Oliver
author_facet Negroni, Caterina
Hilton, David A.
Ercolano, Emanuela
Adams, Claire L.
Kurian, Kathreena M.
Baiz, Daniele
Hanemann, C.Oliver
author_sort Negroni, Caterina
collection PubMed
description BACKGROUND: Meningiomas are the most common primary intracranial tumours. They are classified as grade I, II, and III based on their histopathological features. While most meningiomas can be managed by surgery alone, adjuvant treatment may be required in case of recurrent, or high-grade tumours. To date, chemotherapy has proven ineffective in meningioma patients, reinforcing the need for novel therapeutic targets and molecular biomarkers. METHODS: Using meningioma tissues and in vitro models, we investigated microRNA levels in meningioma samples of different grades, as well as their regulation. Based on this, we also investigated candidate miRNAs expression in serum, and their potential as biomarkers. FINDINGS: We found that miR-497~195 cluster expression in meningioma decreases with increasing malignancy grade, and that Cyclin D1 overexpression correlated with downregulation of the miR-497~195 cluster. GATA binding protein 4, a transcription factor upregulated in malignant meningioma, caused increased cell viability by controlling the expression of the miR-497~195 cluster, resulting in increased Cyclin D1 expression. Accordingly, GATA-4 inhibition via the small-molecule inhibitor NSC140905 restored miR-497~195 cluster expression, resulting in decreased viability, and Cyclin D1 downregulation. Analysis of the miR-497~195 cluster expression in serum exosomes derived from high-grade meningioma patients, revealed lower levels of miR-497 compared to those of benign origin. INTERPRETATION: Our data suggest that GATA-4 could be a novel potential therapeutic target, and miR-497 could serve as a potential non-invasive biomarker for high-grade meningioma.
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spelling pubmed-74526962020-09-02 GATA-4, a potential novel therapeutic target for high-grade meningioma, regulates miR-497, a potential novel circulating biomarker for high-grade meningioma Negroni, Caterina Hilton, David A. Ercolano, Emanuela Adams, Claire L. Kurian, Kathreena M. Baiz, Daniele Hanemann, C.Oliver EBioMedicine Research paper BACKGROUND: Meningiomas are the most common primary intracranial tumours. They are classified as grade I, II, and III based on their histopathological features. While most meningiomas can be managed by surgery alone, adjuvant treatment may be required in case of recurrent, or high-grade tumours. To date, chemotherapy has proven ineffective in meningioma patients, reinforcing the need for novel therapeutic targets and molecular biomarkers. METHODS: Using meningioma tissues and in vitro models, we investigated microRNA levels in meningioma samples of different grades, as well as their regulation. Based on this, we also investigated candidate miRNAs expression in serum, and their potential as biomarkers. FINDINGS: We found that miR-497~195 cluster expression in meningioma decreases with increasing malignancy grade, and that Cyclin D1 overexpression correlated with downregulation of the miR-497~195 cluster. GATA binding protein 4, a transcription factor upregulated in malignant meningioma, caused increased cell viability by controlling the expression of the miR-497~195 cluster, resulting in increased Cyclin D1 expression. Accordingly, GATA-4 inhibition via the small-molecule inhibitor NSC140905 restored miR-497~195 cluster expression, resulting in decreased viability, and Cyclin D1 downregulation. Analysis of the miR-497~195 cluster expression in serum exosomes derived from high-grade meningioma patients, revealed lower levels of miR-497 compared to those of benign origin. INTERPRETATION: Our data suggest that GATA-4 could be a novel potential therapeutic target, and miR-497 could serve as a potential non-invasive biomarker for high-grade meningioma. Elsevier 2020-08-15 /pmc/articles/PMC7452696/ /pubmed/32810829 http://dx.doi.org/10.1016/j.ebiom.2020.102941 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research paper
Negroni, Caterina
Hilton, David A.
Ercolano, Emanuela
Adams, Claire L.
Kurian, Kathreena M.
Baiz, Daniele
Hanemann, C.Oliver
GATA-4, a potential novel therapeutic target for high-grade meningioma, regulates miR-497, a potential novel circulating biomarker for high-grade meningioma
title GATA-4, a potential novel therapeutic target for high-grade meningioma, regulates miR-497, a potential novel circulating biomarker for high-grade meningioma
title_full GATA-4, a potential novel therapeutic target for high-grade meningioma, regulates miR-497, a potential novel circulating biomarker for high-grade meningioma
title_fullStr GATA-4, a potential novel therapeutic target for high-grade meningioma, regulates miR-497, a potential novel circulating biomarker for high-grade meningioma
title_full_unstemmed GATA-4, a potential novel therapeutic target for high-grade meningioma, regulates miR-497, a potential novel circulating biomarker for high-grade meningioma
title_short GATA-4, a potential novel therapeutic target for high-grade meningioma, regulates miR-497, a potential novel circulating biomarker for high-grade meningioma
title_sort gata-4, a potential novel therapeutic target for high-grade meningioma, regulates mir-497, a potential novel circulating biomarker for high-grade meningioma
topic Research paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452696/
https://www.ncbi.nlm.nih.gov/pubmed/32810829
http://dx.doi.org/10.1016/j.ebiom.2020.102941
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