研究动态
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探究阿霉素在宫颈癌中的作用机制:转录组学和代谢组学视角的融合。

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

发表日期:2023
作者: Zhuo Huang, Huining Jing, Juanjuan Lv, Yan Chen, YuanQiong Huang, Shuwen Sun
来源: Frontiers in Genetics

摘要:

引言:宫颈癌仍然是全球健康负担的重要问题,阿霉素是针对该病的重要治疗药物。然而,其治疗效应的精确分子机制尚未完全理解。方法:本研究采用多组学方法,将转录组和代谢组学分析与细胞和体内实验证明结合起来,全面调查与阿霉素治疗宫颈癌相关的分子景观。结果:无偏差差异基因表达分析揭示了阿霉素治疗后基因表达模式的明显变化。值得注意的是,ANKRD18B基因在对阿霉素的反应中扮演了显著角色。同时,我们的代谢组学分析显示了代谢物谱中的显著干扰,特别是对L-鸟氨酸的关注。ANKRD18B基因表达与L-鸟氨酸水平之间的相关性表明存在着严密控制的基因-代谢物网络。通过严格的细胞和体内实验证明了这些结果,并显示在皮下肿瘤大小减小以及ANKRD18B,L-鸟氨酸和阿霉素浓度显著变化。讨论:本研究的发现强调了在阿霉素治疗中转录组和代谢组学变化之间的错综复杂关系。这些发现可能对开发更有效的宫颈癌治疗策略具有重要意义。鉴于ANKRD18B和L-鸟氨酸被确定为该过程的关键组分,未来的研究旨在解析支持阿霉素疗效的复杂分子网络。虽然本研究提供了坚实的基础,但也强调了进一步研究以充分了解这些相互作用及其对宫颈癌治疗的潜在意义的必要性。版权所有 © 2023黄,敬,吕,陈,黄和孙。
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.Copyright © 2023 Huang, Jing, Lv, Chen, Huang and Sun.