Qi Su1
Francesca Maria Orlandella
Giovanni Smaldone
Yitao Qi- 1Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest China, College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi, China
- 2University of Naples Parthenope, Naples, Italy
- 3IRCCS SYNLAB SDN, Naples, Italy
Editorial on the Research Topic
LncRNA and their role on epigenome in cancer
In this Research Topic “LncRNA and their role on epigenome in cancer”, a series of original comprehensive studies and reviews were collected, that describe the critical role of LncRNA (long non-coding RNA) in the regulation of cancer. LncRNAs refer to non-protein-coding RNA molecules with a length of more than 200 bp (Srinivas et al., 2024; Zhang, 2024). More studies have shown that LncRNAs play an important role in the regulation of gene expression at the epigenetic, transcriptional, and post-transcriptional levels (Luo et al., 2021; Yang et al., 2022), and are closely associated with the occurrence and development of cancer (Toden et al., 2021). Therefore, LncRNAs are likely to become a potential target for clinical treatment of cancer, and the establishment of LncRNA based therapy has broad prospects in exploring the pathogenesis of cancer. Besides their therapeutic potential, the knowledgement of circulating LncRNAs could be crucial for the develop of novel minimally invasive diagnostic and prognostic strategy in cancer patients since, when are released in the blood, they are stable and free from nuclease degradation. In view of the important regulatory role of LncRNA in cancer and the latest research progress in this field, we organized this study to comprehensively summarize the new mechanisms, potential and obstacles of LncRNA in regulating tumor development. The following is the summary of the original research and reviews from each contributor for this Research Topic of “LncRNA and their role on epigenome in cancer.”
In the first article in Research Topic, Chi et al. used medical big data and artificial intelligence to construct a prediction model of disulfidptosis response-related LncRNA on the TCGA-COAD cohort, and identified that disulfidptosis response-related LncRNA were a robust predictors of colon adenocarcinoma (COAD). The model facilitated the precise classification of clinical COAD patients and identified specific subgroups that are more beneficial to immunotherapy and chemotherapy, providing favorable information for the development of personalized treatment strategies for COAD patients. In this study, these LncRNAs were evaluated as independent prognostic factors for COAD, and patients in the low-risk group showed higher overall survival, providing new insights into immunotherapy response and prognosis assessment in COAD. In conclusion, this study successfully identified specific LncRNAs that are closely associated with death by disulfide, revealing new prognostic biomarkers and potential therapeutic targets of COAD.
In the next article, Moaveni et al. provide a comprehensive and critical analysis of recent advances and challenges in gene therapy for pediatric cancer. The challenges facing pediatric cancer are more unique and complex than those facing adult cancers. This review elucidates current innovative systems that promise to address pediatric tumors, such as viral platforms (retroviruses, lentiviruses, adeno-associated viruses), non-viral platforms (liposomes, nanoparticles), and immunotherapies (CAR T-cell therapy, tumor-targeting antibodies, checkpoint inhibitors), and discussed the barriers and challenges posed by pediatric cancer to gene therapy. In addition, the authors conduct a comprehensive analysis of ethical and clinical model studies to provide valuable insights into gene therapy for pediatric cancer. In summary, this review summarizes the latest overview of gene therapy in pediatric cancer, highlights rapid scientific progress and substantial barriers to be addressed, and proposes gene therapy as a treatment available to pediatric patients worldwide.
In the third article in this Research Topic, Wei et al. reviewed the differential expression and clinical significance of LncRNA in the development and progression of lung adenocarcinoma (LUAD). LncRNA can regulate the occurrence and development of tumors, and are considered as one of the research hotspots in human LUAD and other malignant tumors. The authors first introduced the function and research status of LncRNA, and summarized the regulatory mechanism of LncRNA in LUAD and the influence of differential expression of LncRNA on the progress of LUAD. Subsequently, the authors described the signal transduction pathways of LncRNA involved in LUAD, including JAK/STAT, PI3K/Akt/mTOR, Wnt/β-catenin, TGF-β/SMAD, and ATR/CHK1 signaling pathways and miRNA signaling axis. A comprehensive summary of the close relationship between LncRNA and LUAD provides a novel idea for the early diagnosis and treatment of LUAD.
Glutathione peroxidase 4 (GPX4) is a unique antioxidant enzyme that can protect cells from membrane lipid peroxidation and maintain redox homeostasis, and its role in patients with hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) was studied (Su et al.). In 289 participants, GPX4 expression levels in serum and peripheral blood mononuclear cells (PBMCs) of HBV-ACLF patients were lower than in non-HBV ACLF patients, chronic hepatitis B (CHB) and healthy control (HC) individuals. At the same time, in HBV-ACLF patients, the methylation level of GPX4 promoter is higher, and it is related to oxidative stress and inflammation related molecules. The methylation level of the GPX4 promoter, as assessed by the ROC curve, was identified as a biomarker for predicting 90-day mortality in HBV-ACLF patients. This study shows the importance of GPX4 in HBV-ACLF, which provides new ideas for the clinical treatment and prognosis of HBV-ACLF, and the specific regulatory mechanism needs to be further explored.
Finally, in this Research Topic, based on the correlation between the basement membrane and related LncRNA and the prognosis of head and neck squamous cell carcinoma (HNSCC), Bu et al. first used the Cancer Genome Atlas (TCGA) database to obtain HNSCC related data. In this study, differentially expressed LncRNAs were screened, and a basement membrane LncRNA-based prognostic model was successfully established and comprehensively analyzed from different perspectives. By establishing a risk model, 14 pairs of basement membrane LncRNA were evaluated comprehensively, indicating that risk assessment can be used as a reliable prognostic factor. If in vitro and in vivo studies can be combined at a later stage, it will be more helpful to explore new targets for head and neck squamous cell carcinoma (HNSCC) treatment, and provide clinical guidance for clinical research and drug development.
The incidence and mortality of cancer are increasing year by year, and it has become the main cause threatening human life and health worldwide (He et al., 2023; Schwartz, 2024). In recent years, gene therapy approaches have become a new way of clinical treatment of cancer, such as CRISPR system has been widely used in cancer-related basic research (Schambach et al., 2024). Targeting gene mutations that drive tumor growth and spread provide new possibilities for the development of more effective and personalized cancer treatment (Chehelgerdi et al., 2024). With the application of gene editing technology, a large number of LncRNA have been found to play important regulatory roles in cancer, including participating in chromatin modification, genomic imprinting, and intranuclear transport (Kopp and Mendell, 2018; Liu et al., 2024). In addition, immunotherapy and other methods by regulating DNA levels are gradually being developed. In conclusion, this Research Topic confirmed that the differential expression of LncRNA is closely related to the development of cancer, but the specific regulatory mechanism of LncRNA in cancer has been studied with further challenges. Therefore, as the potential mechanisms of LncRNA in the occurrence and development of cancer continue to be explored, future studies are expected to develop various cancer-related LncRNA, providing new targets for the early diagnosis and clinical treatment of cancer.
Author contributions
QS: Writing–original draft, Writing–review and editing. FMO: Writing–review and editing. GS: Writing–review and editing. YQ: Writing–original draft, Writing–review and editing.
Funding
The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. We thank the grants from the National Natural Science Foundation of China (81870241, 82273395, and 82203387), the Fundamental Research Funds for the Central Universities (GK202202006, GK202207003), the Shaanxi Province Postdoctoral Science Foundation (2023BSHYDZZ117), the Excellent Graduate Training Program of Shaanxi Normal University (LHRCTS23089, LHRCCX23174), the Macao Youth Scholars Program (AM2022017), and the grant of the Italian Ministry of Health (GR-2021-12372945).
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
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References
Chehelgerdi, M., Chehelgerdi, M., Khorramian-Ghahfarokhi, M., Shafieizadeh, M., Mahmoudi, E., Eskandari, F., et al. (2024). Comprehensive review of CRISPR-based gene editing: mechanisms, challenges, and applications in cancer therapy. Mol. Cancer 23, 9, doi:10.1186/s12943-023-01925-5
He, S., Xia, C., Li, H., Cao, M., Yang, F., Yan, X., et al. (2023). Cancer profiles in China and comparisons with the USA: a comprehensive analysis in the incidence, mortality, survival, staging, and attribution to risk factors. Sci. China Life Sci. 67, 122–131. doi:10.1007/s11427-023-2423-1
Kopp, F., and Mendell, J. T. (2018). Functional Classification and Experimental Dissection of Long Noncoding RNAs. Cell 172, 393–407. doi:10.1016/j.cell.2018.01.011
Liu, C., Shen, A., Song, J., Cheng, L., Zhang, M., Wang, Y., et al. (2024). LncRNA-CCAT5-mediated crosstalk between Wnt/β-Catenin and STAT3 signaling suggests novel therapeutic approaches for metastatic gastric cancer with high Wnt activity. Cancer Commun. d 44, 76–100. doi:10.1002/cac2.12507
Luo, Y., Zheng, S., Wu, Q., Wu, J., Zhou, R., Wang, C., et al. (2021). Long noncoding RNA (lncRNA) EIF3J-DT induces chemoresistance of gastric cancer via autophagy activation. Autophagy 17, 4083–4101. doi:10.1080/15548627.2021.1901204
Schambach, A., Buchholz, C. J., Torres-Ruiz, R., Cichutek, K., Morgan, M., Trapani, I., et al. (2024). A new age of precision gene therapy. Lancet 403, 568–582. doi:10.1016/S0140-6736(23)01952-9
Schwartz, S. M. (2024). Epidemiology of cancer. Clin. Chem. 70, 140–149. doi:10.1093/clinchem/hvad202
Srinivas, T., Siqueira, E., and Guil, S. (2024). Techniques for investigating lncRNA transcript functions in neurodevelopment. Mol. Psychiatry 29, 874–890. doi:10.1038/s41380-023-02377-5
Toden, S., Zumwalt, T. J., and Goel, A. (2021). Non-coding RNAs and potential therapeutic targeting in cancer. Biochim. Biophys. Acta Rev. Cancer 1875, 188491, doi:10.1016/j.bbcan.2020.188491
Yang, H., Hu, Y., Weng, M., Liu, X., Wan, P., Hu, Y., et al. (2022). Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer. J. Adv. Res. 37, 91–106. doi:10.1016/j.jare.2021.10.001
Keywords: lncRNA, cancer, gene therapy, gene editing technology, biomarkers, epigenetic
Citation: Su Q, Orlandella FM, Smaldone G and Qi Y (2024) Editorial: LncRNA and their role on epigenome in cancer. Front. Mol. Biosci. 11:1533057. doi: 10.3389/fmolb.2024.1533057
Received: 23 November 2024; Accepted: 26 November 2024;
Published: 04 December 2024.
Edited and reviewed by:
Matteo Becatti, University of Firenze, ItalyCopyright © 2024 Su, Orlandella, Smaldone and Qi. 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: Francesca Maria Orlandella, ZnJhbmNlc2NhbWFyaWEub3JsYW5kZWxsYUB1bmlwYXJ0aGVub3BlLml0; Giovanni Smaldone, Z2lvdmFubmkuc21hbGRvbmVAc3lubGFiLml0; Yitao Qi, cWl5aXRhb0Bzbm51LmVkdS5jbg==