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MicroRNA-138 Increases Chemo-Sensitivity of Glioblastoma through Downregulation of Survivin

Glioblastoma (GBM) is one of the most deadly cancers and poorly responses to chemotherapies, such as temozolomide (TMZ). Dysregulation of intrinsic signaling pathways in cancer cells are often resulted by dysregulated tumor suppressive microRNAs (miRNAs). Previously, we found miR-138 as one of tumor...

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Autores principales: Yoo, Ji-Young, Yeh, Margaret, Wang, Yin-Ying, Oh, Christina, Zhao, Zhong-Ming, Kaur, Balveen, Lee, Tae-Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301402/
https://www.ncbi.nlm.nih.gov/pubmed/34356844
http://dx.doi.org/10.3390/biomedicines9070780
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author Yoo, Ji-Young
Yeh, Margaret
Wang, Yin-Ying
Oh, Christina
Zhao, Zhong-Ming
Kaur, Balveen
Lee, Tae-Jin
author_facet Yoo, Ji-Young
Yeh, Margaret
Wang, Yin-Ying
Oh, Christina
Zhao, Zhong-Ming
Kaur, Balveen
Lee, Tae-Jin
author_sort Yoo, Ji-Young
collection PubMed
description Glioblastoma (GBM) is one of the most deadly cancers and poorly responses to chemotherapies, such as temozolomide (TMZ). Dysregulation of intrinsic signaling pathways in cancer cells are often resulted by dysregulated tumor suppressive microRNAs (miRNAs). Previously, we found miR-138 as one of tumor suppressive miRNAs that were significantly down-regulated in GBM. In this study, we demonstrated that ectopic over-expression of miR-138 sensitizes GBM cells to the treatment of TMZ and increased apoptotic cell death. Mechanistically, miR-138 directly repressed the expression of Survivin, an anti-apoptotic protein, to enhance caspase-induced apoptosis upon TMZ treatment. Using an intracranial GBM xenograft mice model, we also showed that combination of miR-138 with TMZ increases survival rates of the mice compared to the control mice treated with TMZ alone. This study provides strong preclinical evidence of the therapeutic benefit from restoration of miR-138 to sensitize the GBM tumor to conventional chemotherapy.
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spelling pubmed-83014022021-07-24 MicroRNA-138 Increases Chemo-Sensitivity of Glioblastoma through Downregulation of Survivin Yoo, Ji-Young Yeh, Margaret Wang, Yin-Ying Oh, Christina Zhao, Zhong-Ming Kaur, Balveen Lee, Tae-Jin Biomedicines Article Glioblastoma (GBM) is one of the most deadly cancers and poorly responses to chemotherapies, such as temozolomide (TMZ). Dysregulation of intrinsic signaling pathways in cancer cells are often resulted by dysregulated tumor suppressive microRNAs (miRNAs). Previously, we found miR-138 as one of tumor suppressive miRNAs that were significantly down-regulated in GBM. In this study, we demonstrated that ectopic over-expression of miR-138 sensitizes GBM cells to the treatment of TMZ and increased apoptotic cell death. Mechanistically, miR-138 directly repressed the expression of Survivin, an anti-apoptotic protein, to enhance caspase-induced apoptosis upon TMZ treatment. Using an intracranial GBM xenograft mice model, we also showed that combination of miR-138 with TMZ increases survival rates of the mice compared to the control mice treated with TMZ alone. This study provides strong preclinical evidence of the therapeutic benefit from restoration of miR-138 to sensitize the GBM tumor to conventional chemotherapy. MDPI 2021-07-06 /pmc/articles/PMC8301402/ /pubmed/34356844 http://dx.doi.org/10.3390/biomedicines9070780 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Article
Yoo, Ji-Young
Yeh, Margaret
Wang, Yin-Ying
Oh, Christina
Zhao, Zhong-Ming
Kaur, Balveen
Lee, Tae-Jin
MicroRNA-138 Increases Chemo-Sensitivity of Glioblastoma through Downregulation of Survivin
title MicroRNA-138 Increases Chemo-Sensitivity of Glioblastoma through Downregulation of Survivin
title_full MicroRNA-138 Increases Chemo-Sensitivity of Glioblastoma through Downregulation of Survivin
title_fullStr MicroRNA-138 Increases Chemo-Sensitivity of Glioblastoma through Downregulation of Survivin
title_full_unstemmed MicroRNA-138 Increases Chemo-Sensitivity of Glioblastoma through Downregulation of Survivin
title_short MicroRNA-138 Increases Chemo-Sensitivity of Glioblastoma through Downregulation of Survivin
title_sort microrna-138 increases chemo-sensitivity of glioblastoma through downregulation of survivin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301402/
https://www.ncbi.nlm.nih.gov/pubmed/34356844
http://dx.doi.org/10.3390/biomedicines9070780
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