Xiao Zhu
Zhenhua Xu
Biaoru Li4*- 1Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Guangdong Medical University, Zhanjiang, China
- 2Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou Medical College, Hangzhou, China
- 3Center for Cancer and Immunology, Children’s National Health System, Washington, DC, United States
- 4Cancer Center, Medical College of Georgia, Augusta University, Augusta, GA, United States
Editorial on the Research Topic
Epigenetics in cancer: mechanisms and drug development-volume II
Cancer remains the leading cause of death in affluent nations, underscoring the urgent need for innovative approaches to combat this devastating disease (Siegel et al., 2023). Epigenetics, a field of study focusing on the modulation of gene expression and function without altering the DNA sequence, holds tremendous promise in understanding and addressing cancer development and progression.
The Research Topic titled “Epigenetics in Cancer: Mechanisms and Drug Development-volume II” presents a compilation of ten articles contributed by over sixty esteemed authors in the fields of cancer epigenetics and therapeutics. This comprehensive collection encompasses diverse research directions, including the roles of transcription and chromatin in gene regulation, DNA modifications, RNA epigenetics, non-coding RNA, and epigenomic methods. Alongside shedding light on the latest discoveries regarding epigenetic mechanisms, these articles also emphasize novel and promising therapeutic drugs aimed at reversing specific epigenetic alterations.
DNA methylation, a key epigenetic modification, has been extensively studied due to its involvement in transcriptional inhibition and gene silencing (Liang et al., 2021). Recent investigations have elucidated the downstream mechanisms of gene silencing mediated by DNA methylation, uncovering the remarkable contribution of molecular domain proteins (Wurster et al., 2021). In hepatocellular carcinoma (HCC), the understanding of epigenetic abnormalities linked to aberrant enhancers provides novel insights into drug therapy for this malignancy. It has been observed that DNA methylation can finely tune gene expression by balancing the effects of transcriptional inhibition and activation, highlighting its role in gene repression (Goncharova et al., 2023).
For instance, Yang et al. demonstrated the involvement of promoter methylation and miR-454-3p in the dysregulation of 4.1N/EPB41L1 at the transcriptional and posttranscriptional levels, respectively. These findings support the potential therapeutic use of targeting DNA methylation and miR-454-3p for NSCLC treatment. Additionally, Huang et al. analyzed epigenomic and transcriptomic data, proposing a prognostic signature based on six AE-DEGs that outperforms previous models in predicting long-term and short-term overall survival in HCC patients. Their discovery of the unique role of epigenetic aberration-induced aberrant enhancers in HCC progression offers new insights for drug therapy.
RNA methylation, another significant epigenetic modification, has emerged as a major focus of research. With over 100 chemical modification methods identified, N6-methyladenine (m6A) stands out as a predominant RNA modification (Zhou et al., 2020). Studies have highlighted the reversible nature of m6A modification, controlled by writers, readers, and demethylases. M6A plays a critical role in regulating gene expression, splicing, RNA editing, RNA stability, and controlling mRNA lifetime and degradation (Li et al., 2023; Xiong et al., 2023). Notably, the clinical and prognostic value of m6A-related features has been elucidated in glioblastoma multiforme (GBM), laying a foundation for future research in glioma (Liu et al.). Furthermore, researchers have emphasized the potential of ncRNA m6A modification and m6A regulators as promising diagnostic and prognostic biomarkers across various cancers, aiding in recurrence and survival prediction, and serving as potential therapeutic targets in cancer treatment (Chen et al. and Mobet et al.). However, while these advancements offer significant promise, further exploration is necessary to unravel more specific mechanisms and develop theories closer to practical applications in clinical diagnosis and treatment.
Another crucial post-transcriptional modification, 5-methylcytosine (m5C), has demonstrated a pivotal role in gene expression and RNA stability. In hepatocellular HCC, the characterization of m5C-related regulators has enhanced our understanding of the tumor immune landscape and provides a practical tool for predicting prognosis (Liu et al.). This valuable insight has the potential to improve patient outcomes and guide effective interventions for this challenging disease.
Although epigenetic modifiers have shown promise as targets for cancer treatment, their efficacy as standalone therapies remain limited. Combinatorial approaches that integrate epigenetic therapies with other anti-tumor treatments offer a more comprehensive strategy for maximizing therapeutic outcomes (Ye et al., 2021; Li et al., 2022; Lin et al., 2023).
In conclusion, the study of epigenetics in cancer has unveiled intricate mechanisms and opened new avenues for drug development. This collection of articles provides a snapshot of the latest research, encompassing diverse aspects of epigenetic regulation in cancer. As scientists delve deeper into these mechanisms and translate their findings into clinical practice, we anticipate further breakthroughs that will transform the landscape of cancer treatment and improve patient outcomes.
Author contributions
XZ, ZX, and BL conceived the work. XZ wrote and drafted the manuscript. All authors contributed to the article and approved the submitted version.
Acknowledgments
Thanks to all authors who contributed to our Research Topic.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
Goncharova, I. A., Zarubin, A. A., Babushkina, N. P., Koroleva, I. A., and Nazarenko, M. S. (2023). Changes in DNA methylation profile in liver tissue during progression of HCV-induced fibrosis to hepatocellular carcinoma. Vavilovskii Zhurnal Genet. Sel. 27, 72–82. doi:10.18699/VJGB-23-10
Li, X., Li, M., Huang, M., Lin, Q., Fang, Q., Liu, J., et al. (2022). The multi-molecular mechanisms of tumor-targeted drug resistance in precision medicine. Biomed. Pharmacother. 150, 113064. doi:10.1016/j.biopha.2022.113064
Li, Y., Yi, Y., Lv, J., Gao, X., Yu, Y., Babu, S. S., et al. (2023). Low RNA stability signifies increased post-transcriptional regulation of cell identity genes. Nucleic Acids Res., gkad300. Online ahead of print. doi:10.1093/nar/gkad300
Liang, R., Li, X., Li, W., Zhu, X., and Li, C. (2021). DNA methylation in lung cancer patients: Opening a "window of life" under precision medicine. Biomed. Pharmacother. 144, 112202. doi:10.1016/j.biopha.2021.112202
Lin, Q., Zhang, M., Kong, Y., Huang, Z., Zou, Z., Xiong, Z., et al. (2023). Risk score = LncRNAs associated with doxorubicin metabolism can be used as molecular markers for immune microenvironment and immunotherapy in non-small cell lung cancer. Heliyon 9, e13811. doi:10.1016/j.heliyon.2023.e13811
Siegel, R. L., Miller, K. D., Wagle, N. S., and Jemal, A. (2023). Cancer statistics, 2023. CA Cancer J. Clin. 73, 17–48. doi:10.3322/caac.21763
Wurster, K. D., Costanza, M., Kreher, S., Glaser, S., Lamprecht, B., Schleussner, N., et al. (2021). Aberrant expression of and cell death induction by engagement of the MHC-II chaperone CD74 in anaplastic large cell lymphoma (ALCL). Cancers (Basel) 13, 5012. doi:10.3390/cancers13195012
Xiong, Z., Han, Z., Pan, W., Zhu, X., and Liu, C. (2023). Correlation between chromatin epigenetic-related lncRNA signature (CELncSig) and prognosis, immune microenvironment, and immunotherapy in non-small cell lung cancer. PLoS One 18, 0286122. doi:10.1371/journal.pone.0286122
Ye, Z., Huang, Y., Ke, J., Zhu, X., Leng, S., and Luo, H. (2021). Breakthrough in targeted therapy for non-small cell lung cancer. Biomed. Pharmacother. 133, 111079. doi:10.1016/j.biopha.2020.111079
Keywords: editorial, epigenetics, cancer, DNA methylation, RNA methylation
Citation: Zhu X, Xu Z and Li B (2023) Editorial: Epigenetics in cancer: mechanisms and drug development-volume II. Front. Genet. 14:1242960. doi: 10.3389/fgene.2023.1242960
Received: 20 June 2023; Accepted: 21 June 2023;
Published: 05 July 2023.
Edited and reviewed by:
Michael E. Symonds, University of Nottingham, United KingdomCopyright © 2023 Zhu, Xu and Li. 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.
*Correspondence: Zhenhua Xu, zxu@childrensnational.org; Biaoru Li, bli@augusta.edu