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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...

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Autores principales: Bozsodi, Arpad, Scholtz, Beata, Papp, Gergo, Sapi, Zoltan, Biczo, Adam, Varga, Peter Pal, Lazary, Aron
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
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.
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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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