Das Dipanwita, Karthik Nandini, Taneja Reshma
Department of Physiology, Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Front Cell Dev Biol. 2021 Nov 24;9:756458. doi: 10.3389/fcell.2021.756458. eCollection 2021.
Inflammation is an intricate immune response against infection and tissue damage. While the initial immune response is important for preventing tumorigenesis, chronic inflammation is implicated in cancer pathogenesis. It has been linked to various stages of tumor development including transformation, proliferation, angiogenesis, and metastasis. Immune cells, through the production of inflammatory mediators such as cytokines, chemokines, transforming growth factors, and adhesion molecules contribute to the survival, growth, and progression of the tumor in its microenvironment. The aberrant expression and secretion of pro-inflammatory and growth factors by the tumor cells result in the recruitment of immune cells, thus creating a mutual crosstalk. The reciprocal signaling between the tumor cells and the immune cells creates and maintains a successful tumor niche. Many inflammatory factors are regulated by epigenetic mechanisms including DNA methylation and histone modifications. In particular, DNA and histone methylation are crucial forms of transcriptional regulation and aberrant methylation has been associated with deregulated gene expression in oncogenesis. Such deregulations have been reported in both solid tumors and hematological malignancies. With technological advancements to study genome-wide epigenetic landscapes, it is now possible to identify molecular mechanisms underlying altered inflammatory profiles in cancer. In this review, we discuss the role of DNA and histone methylation in regulation of inflammatory pathways in human cancers and review the merits and challenges of targeting inflammatory mediators as well as epigenetic regulators in cancer.
炎症是针对感染和组织损伤的复杂免疫反应。虽然初始免疫反应对于预防肿瘤发生很重要，但慢性炎症与癌症发病机制有关。它与肿瘤发展的各个阶段相关，包括转化、增殖、血管生成和转移。免疫细胞通过产生细胞因子、趋化因子、转化生长因子和黏附分子等炎症介质，在肿瘤微环境中促进肿瘤的存活、生长和进展。肿瘤细胞促炎因子和生长因子的异常表达与分泌导致免疫细胞的募集，从而形成相互的串扰。肿瘤细胞与免疫细胞之间的相互信号传导创造并维持了一个成功的肿瘤微环境。许多炎症因子受表观遗传机制调控，包括DNA甲基化和组蛋白修饰。特别是，DNA和组蛋白甲基化是转录调控的关键形式，异常甲基化与肿瘤发生中基因表达失调有关。实体瘤和血液系统恶性肿瘤中均有此类失调的报道。随着研究全基因组表观遗传图谱的技术进步，现在有可能确定癌症中炎症谱改变的分子机制。在本综述中，我们讨论DNA和组蛋白甲基化在人类癌症炎症途径调控中的作用，并综述针对癌症中炎症介质以及表观遗传调节因子的优点和挑战。
