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Investigating Doxorubicin’s mechanism of action in cervical cancer: a convergence of transcriptomic and metabolomic perspectives

Introduction: Cervical cancer remains a significant global health burden, and Doxorubicin is a crucial therapeutic agent against this disease. However, the precise molecular mechanisms responsible for its therapeutic effects are not fully understood. Methods: In this study, we employed a multi-omics...

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Autores principales: Huang, Zhuo, Jing, Huining, Lv, Juanjuan, Chen, Yan, Huang, YuanQiong, Sun, Shuwen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10494242/
https://www.ncbi.nlm.nih.gov/pubmed/37701623
http://dx.doi.org/10.3389/fgene.2023.1234263
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author Huang, Zhuo
Jing, Huining
Lv, Juanjuan
Chen, Yan
Huang, YuanQiong
Sun, Shuwen
author_facet Huang, Zhuo
Jing, Huining
Lv, Juanjuan
Chen, Yan
Huang, YuanQiong
Sun, Shuwen
author_sort Huang, Zhuo
collection PubMed
description Introduction: Cervical cancer remains a significant global health burden, and Doxorubicin is a crucial therapeutic agent against this disease. However, the precise molecular mechanisms responsible for its therapeutic effects are not fully understood. Methods: In this study, we employed a multi-omics approach that combined transcriptomic and metabolomic analyses with cellular and in vivo experiments. The goal was to comprehensively investigate the molecular landscape associated with Doxorubicin treatment in cervical cancer. Results: Our unbiased differential gene expression analysis revealed distinct alterations in gene expression patterns following Doxorubicin treatment. Notably, the ANKRD18B gene exhibited a prominent role in the response to Doxorubicin. Simultaneously, our metabolomic analysis demonstrated significant perturbations in metabolite profiles, with a particular focus on L-Ornithine. The correlation between ANKRD18B gene expression and L-Ornithine levels indicated a tightly controlled gene-metabolite network. These results were further confirmed through rigorous cellular and in vivo experiments, which showed reductions in subcutaneous tumor size and significant changes in ANKRD18B, L-Ornithine, and Doxorubicin concentration. Discussion: The findings of this study underscore the intricate interplay between transcriptomic and metabolomic changes in response to Doxorubicin treatment. These insights could have implications for the development of more effective therapeutic strategies for cervical cancer. The identification of ANKRD18B and L-Ornithine as key components in this process lays the groundwork for future research aiming to unravel the complex molecular networks that underlie Doxorubicin’s therapeutic mechanism. While this study provides a solid foundation, it also highlights the necessity for further investigation to fully grasp these interactions and their potential implications for cervical cancer treatment.
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spelling pubmed-104942422023-09-12 Investigating Doxorubicin’s mechanism of action in cervical cancer: a convergence of transcriptomic and metabolomic perspectives Huang, Zhuo Jing, Huining Lv, Juanjuan Chen, Yan Huang, YuanQiong Sun, Shuwen Front Genet Genetics Introduction: Cervical cancer remains a significant global health burden, and Doxorubicin is a crucial therapeutic agent against this disease. However, the precise molecular mechanisms responsible for its therapeutic effects are not fully understood. Methods: In this study, we employed a multi-omics approach that combined transcriptomic and metabolomic analyses with cellular and in vivo experiments. The goal was to comprehensively investigate the molecular landscape associated with Doxorubicin treatment in cervical cancer. Results: Our unbiased differential gene expression analysis revealed distinct alterations in gene expression patterns following Doxorubicin treatment. Notably, the ANKRD18B gene exhibited a prominent role in the response to Doxorubicin. Simultaneously, our metabolomic analysis demonstrated significant perturbations in metabolite profiles, with a particular focus on L-Ornithine. The correlation between ANKRD18B gene expression and L-Ornithine levels indicated a tightly controlled gene-metabolite network. These results were further confirmed through rigorous cellular and in vivo experiments, which showed reductions in subcutaneous tumor size and significant changes in ANKRD18B, L-Ornithine, and Doxorubicin concentration. Discussion: The findings of this study underscore the intricate interplay between transcriptomic and metabolomic changes in response to Doxorubicin treatment. These insights could have implications for the development of more effective therapeutic strategies for cervical cancer. The identification of ANKRD18B and L-Ornithine as key components in this process lays the groundwork for future research aiming to unravel the complex molecular networks that underlie Doxorubicin’s therapeutic mechanism. While this study provides a solid foundation, it also highlights the necessity for further investigation to fully grasp these interactions and their potential implications for cervical cancer treatment. Frontiers Media S.A. 2023-08-28 /pmc/articles/PMC10494242/ /pubmed/37701623 http://dx.doi.org/10.3389/fgene.2023.1234263 Text en Copyright © 2023 Huang, Jing, Lv, Chen, Huang and Sun. 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 Genetics
Huang, Zhuo
Jing, Huining
Lv, Juanjuan
Chen, Yan
Huang, YuanQiong
Sun, Shuwen
Investigating Doxorubicin’s mechanism of action in cervical cancer: a convergence of transcriptomic and metabolomic perspectives
title Investigating Doxorubicin’s mechanism of action in cervical cancer: a convergence of transcriptomic and metabolomic perspectives
title_full Investigating Doxorubicin’s mechanism of action in cervical cancer: a convergence of transcriptomic and metabolomic perspectives
title_fullStr Investigating Doxorubicin’s mechanism of action in cervical cancer: a convergence of transcriptomic and metabolomic perspectives
title_full_unstemmed Investigating Doxorubicin’s mechanism of action in cervical cancer: a convergence of transcriptomic and metabolomic perspectives
title_short Investigating Doxorubicin’s mechanism of action in cervical cancer: a convergence of transcriptomic and metabolomic perspectives
title_sort investigating doxorubicin’s mechanism of action in cervical cancer: a convergence of transcriptomic and metabolomic perspectives
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10494242/
https://www.ncbi.nlm.nih.gov/pubmed/37701623
http://dx.doi.org/10.3389/fgene.2023.1234263
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