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Role of MYC-miR-29-B7-H3 in Medulloblastoma Growth and Angiogenesis
Medulloblastoma (MB) is the most common embryonal neuroepithelial tumor, with poor patient outcomes and secondary complications. In this study, we investigated the role of the B7 family of immune checkpoint homolog 3 (B7-H3) expression in MB angiogenesis. B7-H3, a co-inhibitory immune checkpoint, is...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723910/ https://www.ncbi.nlm.nih.gov/pubmed/31382461 http://dx.doi.org/10.3390/jcm8081158 |
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author | Purvis, Ian J. Avilala, Janardhan Guda, Maheedhara R. Venkataraman, Sujatha Vibhakar, Rajeev Tsung, Andrew J. Velpula, Kiran K. Asuthkar, Swapna |
author_facet | Purvis, Ian J. Avilala, Janardhan Guda, Maheedhara R. Venkataraman, Sujatha Vibhakar, Rajeev Tsung, Andrew J. Velpula, Kiran K. Asuthkar, Swapna |
author_sort | Purvis, Ian J. |
collection | PubMed |
description | Medulloblastoma (MB) is the most common embryonal neuroepithelial tumor, with poor patient outcomes and secondary complications. In this study, we investigated the role of the B7 family of immune checkpoint homolog 3 (B7-H3) expression in MB angiogenesis. B7-H3, a co-inhibitory immune checkpoint, is highly expressed and is associated with lower overall survival in MYC(+) MB’s. Evidence for a direct transcriptional role of MYC on the B7-H3 gene promoter was confirmed by MYC inhibition and anti-MYC antibody ChIP analysis. Interestingly, MYC inhibition not only downregulated the B7-H3 protein expression, but also rescued miR-29 expression, thus indicating a triangular regulatory relationship between MYC, miR-29, and B7-H3 in Group 3 MB cells. From RNA seq and IPAD assay, we observed a negative feedback loop between miR-29 and MYC that may control B7-H3 expression levels in MB cells. Our studies show that B7-H3 expression levels play a crucial role in promoting MB angiogenesis which can be inhibited by miR-29 overexpression via miR-29-mediated B7-H3 downregulation. The tumor suppressor role of miR-29 is mediated by the activation of JAK/STAT1 signaling that further plays a role in MYC-B7-H3 downregulation in MB. This study highlights B7-H3 as a viable target in MB angiogenesis, and that the expression of miR-29 can inhibit B7-H3 and sensitize MB cells to treatment with MYC-inhibiting drugs. |
format | Online Article Text |
id | pubmed-6723910 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67239102019-09-10 Role of MYC-miR-29-B7-H3 in Medulloblastoma Growth and Angiogenesis Purvis, Ian J. Avilala, Janardhan Guda, Maheedhara R. Venkataraman, Sujatha Vibhakar, Rajeev Tsung, Andrew J. Velpula, Kiran K. Asuthkar, Swapna J Clin Med Article Medulloblastoma (MB) is the most common embryonal neuroepithelial tumor, with poor patient outcomes and secondary complications. In this study, we investigated the role of the B7 family of immune checkpoint homolog 3 (B7-H3) expression in MB angiogenesis. B7-H3, a co-inhibitory immune checkpoint, is highly expressed and is associated with lower overall survival in MYC(+) MB’s. Evidence for a direct transcriptional role of MYC on the B7-H3 gene promoter was confirmed by MYC inhibition and anti-MYC antibody ChIP analysis. Interestingly, MYC inhibition not only downregulated the B7-H3 protein expression, but also rescued miR-29 expression, thus indicating a triangular regulatory relationship between MYC, miR-29, and B7-H3 in Group 3 MB cells. From RNA seq and IPAD assay, we observed a negative feedback loop between miR-29 and MYC that may control B7-H3 expression levels in MB cells. Our studies show that B7-H3 expression levels play a crucial role in promoting MB angiogenesis which can be inhibited by miR-29 overexpression via miR-29-mediated B7-H3 downregulation. The tumor suppressor role of miR-29 is mediated by the activation of JAK/STAT1 signaling that further plays a role in MYC-B7-H3 downregulation in MB. This study highlights B7-H3 as a viable target in MB angiogenesis, and that the expression of miR-29 can inhibit B7-H3 and sensitize MB cells to treatment with MYC-inhibiting drugs. MDPI 2019-08-02 /pmc/articles/PMC6723910/ /pubmed/31382461 http://dx.doi.org/10.3390/jcm8081158 Text en © 2019 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Purvis, Ian J. Avilala, Janardhan Guda, Maheedhara R. Venkataraman, Sujatha Vibhakar, Rajeev Tsung, Andrew J. Velpula, Kiran K. Asuthkar, Swapna Role of MYC-miR-29-B7-H3 in Medulloblastoma Growth and Angiogenesis |
title | Role of MYC-miR-29-B7-H3 in Medulloblastoma Growth and Angiogenesis |
title_full | Role of MYC-miR-29-B7-H3 in Medulloblastoma Growth and Angiogenesis |
title_fullStr | Role of MYC-miR-29-B7-H3 in Medulloblastoma Growth and Angiogenesis |
title_full_unstemmed | Role of MYC-miR-29-B7-H3 in Medulloblastoma Growth and Angiogenesis |
title_short | Role of MYC-miR-29-B7-H3 in Medulloblastoma Growth and Angiogenesis |
title_sort | role of myc-mir-29-b7-h3 in medulloblastoma growth and angiogenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723910/ https://www.ncbi.nlm.nih.gov/pubmed/31382461 http://dx.doi.org/10.3390/jcm8081158 |
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