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Potential molecular mechanism in self-renewal is associated with miRNA dysregulation in sacral chordoma – A next-generation RNA sequencing study
BACKGROUND: Chordoma, the most frequent malignant primary spinal neoplasm, characterized by a high rate of recurrence, is an orphan disease where the clarification of the molecular oncogenesis would be crucial to developing new, effective therapies. Dysregulated expression of non-coding RNAs, especi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9404356/ https://www.ncbi.nlm.nih.gov/pubmed/36033338 http://dx.doi.org/10.1016/j.heliyon.2022.e10227 |
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author | Bozsodi, Arpad Scholtz, Beata Papp, Gergo Sapi, Zoltan Biczo, Adam Varga, Peter Pal Lazary, Aron |
author_facet | Bozsodi, Arpad Scholtz, Beata Papp, Gergo Sapi, Zoltan Biczo, Adam Varga, Peter Pal Lazary, Aron |
author_sort | Bozsodi, Arpad |
collection | PubMed |
description | BACKGROUND: Chordoma, the most frequent malignant primary spinal neoplasm, characterized by a high rate of recurrence, is an orphan disease where the clarification of the molecular oncogenesis would be crucial to developing new, effective therapies. Dysregulated expression of non-coding RNAs, especially microRNAs (miRNA) has a significant role in cancer development. METHODS: Next-generation RNA sequencing (NGS) was used for the combinatorial analysis of mRNA-miRNA gene expression profiles in sacral chordoma and nucleus pulposus samples. Advanced bioinformatics workflow was applied to the data to predict miRNA-mRNA regulatory networks with altered activity in chordoma. RESULTS: A large set of significantly dysregulated miRNAs in chordoma and their differentially expressed target genes have been identified. Several molecular pathways related to tumorigenesis and the modulation of the immune system are predicted to be dysregulated due to aberrant miRNA expression in chordoma. We identified a gene set including key regulators of the Hippo pathway, which is targeted by differently expressed miRNAs, and validated their altered expression by RT-qPCR. These newly identified miRNA/RNA interactions are predicted to have a role in the self-renewal process of chordoma stem cells, which might sustain the high rate of recurrence for this tumor. CONCLUSIONS: Our results can significantly contribute to the designation of possible targets for the development of anti-chordoma therapies. |
format | Online Article Text |
id | pubmed-9404356 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-94043562022-08-26 Potential molecular mechanism in self-renewal is associated with miRNA dysregulation in sacral chordoma – A next-generation RNA sequencing study Bozsodi, Arpad Scholtz, Beata Papp, Gergo Sapi, Zoltan Biczo, Adam Varga, Peter Pal Lazary, Aron Heliyon Research Article BACKGROUND: Chordoma, the most frequent malignant primary spinal neoplasm, characterized by a high rate of recurrence, is an orphan disease where the clarification of the molecular oncogenesis would be crucial to developing new, effective therapies. Dysregulated expression of non-coding RNAs, especially microRNAs (miRNA) has a significant role in cancer development. METHODS: Next-generation RNA sequencing (NGS) was used for the combinatorial analysis of mRNA-miRNA gene expression profiles in sacral chordoma and nucleus pulposus samples. Advanced bioinformatics workflow was applied to the data to predict miRNA-mRNA regulatory networks with altered activity in chordoma. RESULTS: A large set of significantly dysregulated miRNAs in chordoma and their differentially expressed target genes have been identified. Several molecular pathways related to tumorigenesis and the modulation of the immune system are predicted to be dysregulated due to aberrant miRNA expression in chordoma. We identified a gene set including key regulators of the Hippo pathway, which is targeted by differently expressed miRNAs, and validated their altered expression by RT-qPCR. These newly identified miRNA/RNA interactions are predicted to have a role in the self-renewal process of chordoma stem cells, which might sustain the high rate of recurrence for this tumor. CONCLUSIONS: Our results can significantly contribute to the designation of possible targets for the development of anti-chordoma therapies. Elsevier 2022-08-13 /pmc/articles/PMC9404356/ /pubmed/36033338 http://dx.doi.org/10.1016/j.heliyon.2022.e10227 Text en © 2022 The Author(s) https://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 | Research Article Bozsodi, Arpad Scholtz, Beata Papp, Gergo Sapi, Zoltan Biczo, Adam Varga, Peter Pal Lazary, Aron Potential molecular mechanism in self-renewal is associated with miRNA dysregulation in sacral chordoma – A next-generation RNA sequencing study |
title | Potential molecular mechanism in self-renewal is associated with miRNA dysregulation in sacral chordoma – A next-generation RNA sequencing study |
title_full | Potential molecular mechanism in self-renewal is associated with miRNA dysregulation in sacral chordoma – A next-generation RNA sequencing study |
title_fullStr | Potential molecular mechanism in self-renewal is associated with miRNA dysregulation in sacral chordoma – A next-generation RNA sequencing study |
title_full_unstemmed | Potential molecular mechanism in self-renewal is associated with miRNA dysregulation in sacral chordoma – A next-generation RNA sequencing study |
title_short | Potential molecular mechanism in self-renewal is associated with miRNA dysregulation in sacral chordoma – A next-generation RNA sequencing study |
title_sort | potential molecular mechanism in self-renewal is associated with mirna dysregulation in sacral chordoma – a next-generation rna sequencing study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9404356/ https://www.ncbi.nlm.nih.gov/pubmed/36033338 http://dx.doi.org/10.1016/j.heliyon.2022.e10227 |
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