Nwabo Kamdje Armel Hervé, Dongmo Fogang Hervet Paulain, Mimche Patrice N
Department of Physiological Sciences and Biochemistry, Faculty of Medicine and Biomedical Sciences, University of Garoua, Garoua, Cameroon.
Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, United States.
Front Mol Med. 2024 Sep 6;4:1426454. doi: 10.3389/fmmed.2024.1426454. eCollection 2024.
Major epigenetic changes are associated with carcinogenesis, including aberrant DNA methylations and post-translational modifications of histone. Indeed evidence accumulated in recent years indicates that inactivating DNA hypermethylation preferentially targets the subset of polycomb group (PcG) genes that are regulators of developmental processes. Conversely, activating DNA hypomethylation targets oncogenic signaling pathway genes, but outcomes of both events lead in the overexpression of oncogenic signaling pathways that contribute to the stem-like state of cancer cells. On the basis of recent evidence from population-basedclinical and experimental studies, we hypothesize that factors associated with risk for developing a hematologic malignancy (HM), such as metabolic syndrome and chronic inflammation, may trigger epigenetic mechanisms to increase the transcriptional expression of oncogenes and activate oncogenic signaling pathways. Signaling pathways associated with such risk factors include but are not limited to pro-inflammatory nuclear factor κB (NF-κB) and mitogenic, growth, and survival Janus kinase (JAK) intracellular non-receptor tyrosine kinase-triggered pathways. The latter includes signaling pathways such as transducer and activator of transcription (STAT), Ras GTPases/mitogen-activated protein kinases (MAPKs)/extracellular signal-related kinases (ERKs), phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), and β-catenin pathways. Recent findings on epigenetic mechanisms at work in the biology of cancer and in HMs and their importance in the etiology and pathogenesis of these diseases are herein summarized and discussed. Furthermore, the role of epigenetic processes in the determination of biological identity, the consequences for interindividual variability in disease clinical profile, and the potential of epigenetic drugs in HMs are also considered.
主要的表观遗传变化与癌症发生相关，包括异常的DNA甲基化和组蛋白的翻译后修饰。近年来积累的证据确实表明，DNA高甲基化失活优先靶向多梳蛋白家族（PcG）基因的子集，这些基因是发育过程的调节因子。相反，DNA低甲基化激活靶向致癌信号通路基因，但这两种事件的结果都会导致致癌信号通路的过度表达，从而促成癌细胞的干细胞样状态。基于近期基于人群的临床和实验研究证据，我们推测与血液系统恶性肿瘤（HM）发生风险相关的因素，如代谢综合征和慢性炎症，可能触发表观遗传机制，以增加癌基因的转录表达并激活致癌信号通路。与这些风险因素相关的信号通路包括但不限于促炎核因子κB（NF-κB）以及有丝分裂原、生长和存活相关的Janus激酶（JAK）触发的细胞内非受体酪氨酸激酶通路。后者包括信号通路，如信号转导和转录激活因子（STAT）、Ras鸟苷三磷酸酶/丝裂原活化蛋白激酶（MAPK）/细胞外信号调节激酶（ERK）、磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）/雷帕霉素靶蛋白（mTOR）以及β-连环蛋白通路。本文总结并讨论了近期关于表观遗传机制在癌症生物学和血液系统恶性肿瘤中的作用及其在这些疾病病因和发病机制中的重要性的研究结果。此外，还考虑了表观遗传过程在确定生物学特性中的作用、对疾病临床特征个体间变异性的影响以及表观遗传药物在血液系统恶性肿瘤中的潜力。
