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Upregulation of miR181a/miR212 Improves Myogenic Commitment in Murine Fusion-Negative Rhabdomyosarcoma

Fusion-negative rhabdomyosarcoma (FN-RMS) is the most common soft tissue sarcoma of childhood arising from undifferentiated skeletal muscle cells from uncertain origin. Currently used therapies are poorly tumor-specific and fail to tackle the molecular machinery underlying the tumorigenicity and unc...

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Autores principales: Pozzo, Enrico, Giarratana, Nefele, Sassi, Gabriele, Elmastas, Merve, Killian, Theo, Wang, Chao-chi, Marini, Vittoria, Ronzoni, Flavio, Yustein, Jason, Uyttebroeck, Anne, Sampaolesi, Maurilio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378536/
https://www.ncbi.nlm.nih.gov/pubmed/34421639
http://dx.doi.org/10.3389/fphys.2021.701354
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author Pozzo, Enrico
Giarratana, Nefele
Sassi, Gabriele
Elmastas, Merve
Killian, Theo
Wang, Chao-chi
Marini, Vittoria
Ronzoni, Flavio
Yustein, Jason
Uyttebroeck, Anne
Sampaolesi, Maurilio
author_facet Pozzo, Enrico
Giarratana, Nefele
Sassi, Gabriele
Elmastas, Merve
Killian, Theo
Wang, Chao-chi
Marini, Vittoria
Ronzoni, Flavio
Yustein, Jason
Uyttebroeck, Anne
Sampaolesi, Maurilio
author_sort Pozzo, Enrico
collection PubMed
description Fusion-negative rhabdomyosarcoma (FN-RMS) is the most common soft tissue sarcoma of childhood arising from undifferentiated skeletal muscle cells from uncertain origin. Currently used therapies are poorly tumor-specific and fail to tackle the molecular machinery underlying the tumorigenicity and uncontrolled proliferation of FN-RMS. We and other groups recently found that microRNAs (miRNA) network contributes to myogenic epigenetic memory and can influence pluripotent stem cell commitments. Here, we used the previously identified promyogenic miRNAs and tailored it to the murine FN-RMS. Subsequently, we addressed the effects of miRNAs in vivo by performing syngeneic transplant of pre-treated FN-RMS cell line in C57Bl/6 mice. miRNA pre-treatment affects murine FN-RMS cell proliferation in vivo as showed by bioluminescence imaging analysis, resulting in better muscle performances as highlighted by treadmill exhaustion tests. In conclusion, in our study we identified a novel miRNA combination tackling the anti-myogenic features of FN-RMS by reducing proliferation and described novel antitumorigenic therapeutic targets that can be further explored for future pre-clinical applications.
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spelling pubmed-83785362021-08-21 Upregulation of miR181a/miR212 Improves Myogenic Commitment in Murine Fusion-Negative Rhabdomyosarcoma Pozzo, Enrico Giarratana, Nefele Sassi, Gabriele Elmastas, Merve Killian, Theo Wang, Chao-chi Marini, Vittoria Ronzoni, Flavio Yustein, Jason Uyttebroeck, Anne Sampaolesi, Maurilio Front Physiol Physiology Fusion-negative rhabdomyosarcoma (FN-RMS) is the most common soft tissue sarcoma of childhood arising from undifferentiated skeletal muscle cells from uncertain origin. Currently used therapies are poorly tumor-specific and fail to tackle the molecular machinery underlying the tumorigenicity and uncontrolled proliferation of FN-RMS. We and other groups recently found that microRNAs (miRNA) network contributes to myogenic epigenetic memory and can influence pluripotent stem cell commitments. Here, we used the previously identified promyogenic miRNAs and tailored it to the murine FN-RMS. Subsequently, we addressed the effects of miRNAs in vivo by performing syngeneic transplant of pre-treated FN-RMS cell line in C57Bl/6 mice. miRNA pre-treatment affects murine FN-RMS cell proliferation in vivo as showed by bioluminescence imaging analysis, resulting in better muscle performances as highlighted by treadmill exhaustion tests. In conclusion, in our study we identified a novel miRNA combination tackling the anti-myogenic features of FN-RMS by reducing proliferation and described novel antitumorigenic therapeutic targets that can be further explored for future pre-clinical applications. Frontiers Media S.A. 2021-08-06 /pmc/articles/PMC8378536/ /pubmed/34421639 http://dx.doi.org/10.3389/fphys.2021.701354 Text en Copyright © 2021 Pozzo, Giarratana, Sassi, Elmastas, Killian, Wang, Marini, Ronzoni, Yustein, Uyttebroeck and Sampaolesi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Pozzo, Enrico
Giarratana, Nefele
Sassi, Gabriele
Elmastas, Merve
Killian, Theo
Wang, Chao-chi
Marini, Vittoria
Ronzoni, Flavio
Yustein, Jason
Uyttebroeck, Anne
Sampaolesi, Maurilio
Upregulation of miR181a/miR212 Improves Myogenic Commitment in Murine Fusion-Negative Rhabdomyosarcoma
title Upregulation of miR181a/miR212 Improves Myogenic Commitment in Murine Fusion-Negative Rhabdomyosarcoma
title_full Upregulation of miR181a/miR212 Improves Myogenic Commitment in Murine Fusion-Negative Rhabdomyosarcoma
title_fullStr Upregulation of miR181a/miR212 Improves Myogenic Commitment in Murine Fusion-Negative Rhabdomyosarcoma
title_full_unstemmed Upregulation of miR181a/miR212 Improves Myogenic Commitment in Murine Fusion-Negative Rhabdomyosarcoma
title_short Upregulation of miR181a/miR212 Improves Myogenic Commitment in Murine Fusion-Negative Rhabdomyosarcoma
title_sort upregulation of mir181a/mir212 improves myogenic commitment in murine fusion-negative rhabdomyosarcoma
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378536/
https://www.ncbi.nlm.nih.gov/pubmed/34421639
http://dx.doi.org/10.3389/fphys.2021.701354
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