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

Zhuo Huang; Huining Jing; Juanjuan Lv; Yan Chen; YuanQiong Huang; Shuwen Sun

doi:10.3389/fgene.2023.1234263

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

Front Genet. 2023 Aug 28:14:1234263. doi: 10.3389/fgene.2023.1234263. eCollection 2023.

Authors

Zhuo Huang^{1

2

3}, Huining Jing^{2

3

4}, Juanjuan Lv^{1

2}, Yan Chen^{1

2}, YuanQiong Huang⁵, Shuwen Sun^{1

2}

Affiliations

¹ Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
² Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.
³ Department of Medical Genetics, West China Second University Hospital, Sichuan University, Chengdu, China.
⁴ Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.
⁵ Department of Oncology, Luzhou Hospital of Traditional Chinese Medicine, Luzhou, China.

Abstract

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.

Keywords: ANKRD18B; Doxorubicin; L-Ornithine; cervical cancer; metabolomics; multi-omics integration; transcriptomics.