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Impact of miRNA-mRNA Profiling and Their Correlation on Medulloblastoma Tumorigenesis
Medulloblastoma (MB) is a clinically challenging, childhood brain tumor with a diverse genetic makeup and differential miRNA profile. Aiming to identify deregulated miRNAs in MB, the miRNA expression profile of human MB samples was compared to that of normal cerebellar tissues. As a result, 8 upregu...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070673/ https://www.ncbi.nlm.nih.gov/pubmed/30195786 http://dx.doi.org/10.1016/j.omtn.2018.06.004 |
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author | Kumar, Vinod Kumar, Virender Chaudhary, Amit Kumar Coulter, Donald W. McGuire, Timothy Mahato, Ram I. |
author_facet | Kumar, Vinod Kumar, Virender Chaudhary, Amit Kumar Coulter, Donald W. McGuire, Timothy Mahato, Ram I. |
author_sort | Kumar, Vinod |
collection | PubMed |
description | Medulloblastoma (MB) is a clinically challenging, childhood brain tumor with a diverse genetic makeup and differential miRNA profile. Aiming to identify deregulated miRNAs in MB, the miRNA expression profile of human MB samples was compared to that of normal cerebellar tissues. As a result, 8 upregulated and 64 downregulated miRNAs were identified in MB samples. Although various algorithms have been developed to predict the interaction between miRNA-mRNA pairs, the complexity and fidelity of miRNA-mRNA remain a concern. Therefore, to identify the signatures of miRNA-mRNA interactions essential for MB pathogenesis, miRNA profiling, RNA sequencing, and ingenuity pathway analysis (IPA) were performed in the same primary human MB samples. Further, when miR-217 was inhibited, a significant upregulation of predicted target genes SIRT1, ROBO1, FOXO3, and SMAD7 in HDMB03 cells was observed, confirming the validity of our approach. Functional analysis revealed that the inhibition of miR-217 in HDMB03 cells suppresses colony formation, migration, invasion, promoted apoptosis, and arrested cell population in S phase, indicating that manipulation of miR-217 may have a therapeutic potential for MB patients. Therefore, our study provides an essential platform for future investigations of specific miRNAs responsible for MB pathogenesis. |
format | Online Article Text |
id | pubmed-6070673 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-60706732018-08-02 Impact of miRNA-mRNA Profiling and Their Correlation on Medulloblastoma Tumorigenesis Kumar, Vinod Kumar, Virender Chaudhary, Amit Kumar Coulter, Donald W. McGuire, Timothy Mahato, Ram I. Mol Ther Nucleic Acids Article Medulloblastoma (MB) is a clinically challenging, childhood brain tumor with a diverse genetic makeup and differential miRNA profile. Aiming to identify deregulated miRNAs in MB, the miRNA expression profile of human MB samples was compared to that of normal cerebellar tissues. As a result, 8 upregulated and 64 downregulated miRNAs were identified in MB samples. Although various algorithms have been developed to predict the interaction between miRNA-mRNA pairs, the complexity and fidelity of miRNA-mRNA remain a concern. Therefore, to identify the signatures of miRNA-mRNA interactions essential for MB pathogenesis, miRNA profiling, RNA sequencing, and ingenuity pathway analysis (IPA) were performed in the same primary human MB samples. Further, when miR-217 was inhibited, a significant upregulation of predicted target genes SIRT1, ROBO1, FOXO3, and SMAD7 in HDMB03 cells was observed, confirming the validity of our approach. Functional analysis revealed that the inhibition of miR-217 in HDMB03 cells suppresses colony formation, migration, invasion, promoted apoptosis, and arrested cell population in S phase, indicating that manipulation of miR-217 may have a therapeutic potential for MB patients. Therefore, our study provides an essential platform for future investigations of specific miRNAs responsible for MB pathogenesis. American Society of Gene & Cell Therapy 2018-06-19 /pmc/articles/PMC6070673/ /pubmed/30195786 http://dx.doi.org/10.1016/j.omtn.2018.06.004 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kumar, Vinod Kumar, Virender Chaudhary, Amit Kumar Coulter, Donald W. McGuire, Timothy Mahato, Ram I. Impact of miRNA-mRNA Profiling and Their Correlation on Medulloblastoma Tumorigenesis |
title | Impact of miRNA-mRNA Profiling and Their Correlation on Medulloblastoma Tumorigenesis |
title_full | Impact of miRNA-mRNA Profiling and Their Correlation on Medulloblastoma Tumorigenesis |
title_fullStr | Impact of miRNA-mRNA Profiling and Their Correlation on Medulloblastoma Tumorigenesis |
title_full_unstemmed | Impact of miRNA-mRNA Profiling and Their Correlation on Medulloblastoma Tumorigenesis |
title_short | Impact of miRNA-mRNA Profiling and Their Correlation on Medulloblastoma Tumorigenesis |
title_sort | impact of mirna-mrna profiling and their correlation on medulloblastoma tumorigenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070673/ https://www.ncbi.nlm.nih.gov/pubmed/30195786 http://dx.doi.org/10.1016/j.omtn.2018.06.004 |
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