NHC Key Laboratory of Carcinogenesis, National Clinical Research Center for Geriatric Disorders, Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Clinical Medicine, Xingya School of Medicine of Central South University, Changsha, China.
Front Immunol. 2023 Aug 16;14:1227041. doi: 10.3389/fimmu.2023.1227041. eCollection 2023.
Retinoic acid-inducible gene-I (RIG-I) like receptor (RLR) pathway is one of the most significant pathways supervising aberrant RNA in cells. In predominant conditions, the RLR pathway initiates anti-infection function via activating inflammatory effects, while recently it is discovered to be involved in cancer development as well, acting as a virus-mimicry responder. On one hand, the product IFNs induces tumor elimination. On the other hand, the NF-κB pathway is activated which may lead to tumor progression. Emerging evidence demonstrates that a wide range of modifications are involved in regulating RLR pathways in cancer, which either boost tumor suppression effect or prompt tumor development. This review summarized current epigenetic modulations including DNA methylation, histone modification, and ncRNA interference, as well as post-transcriptional modification like m6A and A-to-I editing of the upstream ligand dsRNA in cancer cells. The post-translational modulations like phosphorylation and ubiquitylation of the pathway's key components were also discussed. Ultimately, we provided an overview of the current therapeutic strategies targeting the RLR pathway in cancers.
视黄酸诱导基因-I（RIG-I）样受体（RLR）通路是细胞中监管异常 RNA 的最重要通路之一。在主要条件下，RLR 通路通过激活炎症反应来启动抗感染功能，而最近发现它也参与癌症的发展，作为病毒模拟应答器。一方面，IFNs 的产物诱导肿瘤消除。另一方面，NF-κB 通路被激活，这可能导致肿瘤进展。新出现的证据表明，广泛的修饰参与调节癌症中的 RLR 通路，这些修饰既可以增强肿瘤抑制作用，也可以促进肿瘤发展。本综述总结了目前在癌细胞中涉及上游配体 dsRNA 的 DNA 甲基化、组蛋白修饰和 ncRNA 干扰以及转录后修饰（如 m6A 和 A-to-I 编辑）的表观遗传调控。还讨论了该通路关键成分的翻译后修饰，如磷酸化和泛素化。最后，我们概述了目前针对癌症中 RLR 通路的治疗策略。
