Luo Hao-Yun, Shen Hai-Ying, Perkins R Serene, Wang Ya-Xu
Department of Gastrointestinal and Anorectal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Neuroscience, Legacy Research Institute, Portland, OR, United States.
Front Pharmacol. 2022 Jun 1;13:908882. doi: 10.3389/fphar.2022.908882. eCollection 2022.
Methylation is an important mechanism contributing to cancer pathology. Methylation of tumor suppressor genes and oncogenes has been closely associated with tumor occurrence and development. New insights regarding the potential role of the adenosine receptor-independent pathway in the epigenetic modulation of DNA methylation offer the possibility of new interventional strategies for cancer therapy. Targeting DNA methylation of cancer-related genes is a promising therapeutic strategy; drugs like 5-Aza-2'-deoxycytidine (5-AZA-CdR, decitabine) effectively reverse DNA methylation and cancer cell growth. However, current anti-methylation (or methylation modifiers) are associated with severe side effects; thus, there is an urgent need for safer and more specific inhibitors of DNA methylation (or DNA methylation modifiers). The adenosine signaling pathway is reported to be involved in cancer pathology and participates in the development of tumors by altering DNA methylation. Most recently, an adenosine metabolic clearance enzyme, adenosine kinase (ADK), has been shown to influence methylation on tumor suppressor genes and tumor development and progression. This review article focuses on recent updates on ADK and its two isoforms, and its actions in adenosine receptor-independent pathways, including methylation modification and epigenetic changes in cancer pathology.
甲基化是一种对癌症病理有重要影响的机制。肿瘤抑制基因和癌基因的甲基化与肿瘤的发生和发展密切相关。关于腺苷受体非依赖途径在DNA甲基化表观遗传调控中的潜在作用的新见解为癌症治疗提供了新的干预策略的可能性。靶向癌症相关基因的DNA甲基化是一种有前景的治疗策略；像5-氮杂-2'-脱氧胞苷（5-AZA-CdR，地西他滨）这样的药物能有效逆转DNA甲基化并抑制癌细胞生长。然而，目前的抗甲基化药物（或甲基化修饰剂）存在严重的副作用；因此，迫切需要更安全、更具特异性的DNA甲基化抑制剂（或DNA甲基化修饰剂）。据报道，腺苷信号通路参与癌症病理过程，并通过改变DNA甲基化参与肿瘤的发展。最近，一种腺苷代谢清除酶，腺苷激酶（ADK），已被证明会影响肿瘤抑制基因的甲基化以及肿瘤的发展和进展。这篇综述文章重点关注了ADK及其两种同工型的最新研究进展，以及它在腺苷受体非依赖途径中的作用，包括癌症病理中的甲基化修饰和表观遗传变化。
