Editorial on the Research Topic Epigenetic regulation and non-histone post-translational modification in cancerEpigenetic changes are essentially involved in both normal organism function and disease progression (Deans and Maggert, 2015). Epigenetic regulation includes DNA methylation or demethylation, chromatin remodeling, histone modifications and noncoding RNAs, which are broadly reported to dysfunction in cancer. Of noted, it is increasingly clear that epigenetic regulation parallels with gene expression modulation. Currently, significant progress has been made in the development of drugs targeting key enzymes involved in epigenetic regulation and post-translational modification without histone. Several drugs have been approved for therapeutic application, and many more are in clinical and preclinical testing (Ferreira and Esteller, 2018;Lu et al., 2020). The aim of this Research Topic is to provide an overview of the current understanding and fundamental findings in the field of epigenetic regulation and non-histone post-translational modifications in cancer. We collected 14 articles including the effects of m6A modifications, non-coding RNAs and SELENBP1 in cancer progression.DNA methylation is strongly associated with cancer, and hypermethylation of some genes in the promoter region interferes with the reading of DNA information thereby altering epigenetics, thus it has the potential to be a promising target for cancer therapy (Smith and Meissner, 2013). Liexi Xu et al. used the methylation and clinical data of lung adenocarcinoma (LUAD) patients from TCGA. They found 11 differential methylation genes and established a methylation scoring model to assess prognosis, suggesting that these genes could be used as biomarkers of methylation in LUAD. Dong-Mei Hu et al. focused on the relationship between Forkhead box P (FOXP) family DNA methylation and immunerelated factors in non-small cell lung cancer (NSCLC) patients. FOXP family is widely involved in regulating immune molecules and influencing immune infiltration in NSCLC, and FOXP family DNA methylation is associated with NSCLC prognosis. In addition to lung
Lung cancer is the main cause of cancer-related mortality, of which non-small cell lung cancer (NSCLC) accounts for 85%. Abemaciclib, a selective CDK4/6 inhibitor, enhanced the radiosensitivity of NSCLC in vivo and in vitro and improved the prognosis of advanced NSCLC patients according to a Phase I clinical trial. This study aimed to explore the impact of CDK4/6 inhibition combined with irradiation and immunotherapy on NSCLC. The in vivo xenograft tumor mouse model was used to investigate the synergistic effects of CDK4/6 inhibitor abemaciclib and irradiation together with anti-PD-1 antibodies. The tumor infiltrating lymphocytes (TILs) in tumor microenvironment (TME) were analyzed by flow cytometry. The complete blood count and serum tests were used to determine the safety of this combination therapy. The human phospho-kinase array and dual-luciferase report assay were used to study the regulatory mechanisms of abemaciclib and irradiation combination on PD-L1 transcription in NSCLC cells in vitro. Our results indicated the significantly synergistic effects of abemaciclib, irradiation and anti-PD-1 antibodies on NSCLC growth in vivo, accompanied by increased CD8+ T cell infiltration and decreased regulatory T cells and myeloid-derived suppressor cells (MDSCs), suggesting a strong anti-tumor combination of CDK4/6 inhibition, radiotherapy and immunotherapy. This synergistic effect could be partially impaired by CD8 depletion, and alleviated the anemia and inflammation caused by tumor burden without hepatorenal toxicity. Abemaciclib induced PD-L1 transcription through JNK/c-Jun pathway in vitro, which might elevate PD-L1 expression synergistically with irradiation through TBK1/IRF3 pathway. Our studies suggested that CDK4/6 inhibition plus irradiation enhanced anti-tumor immune responses in NSCLC. Together with immunotherapy, the combination of CDK4/6 inhibitors and radiotherapy could lower the doses of individual treatment, thus alleviating the potential toxicity and side effects of CDK4/6 inhibition and irradiation on normal cells. Citation Format: Zhengrong Huang, Jiang Luo, Mengqin Wang, Hongxin Xie, Yuxin Zeng, Yu Yuan, Wan Xiang, Ziyu Jiang, Conghua Xie, Yan Gong. CDK4/6 inhibition plus radiotherapy enhances anti-tumor immunity in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2811.
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