Roles of RNA-binding proteins in immune diseases and cancer
Roles of RNA-binding proteins in immune diseases and cancer
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DOI：
10.1016/j.semcancer.2022.03.017
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发表时间：
2022-10-14
影响因子：
14.5
通讯作者：
Kishimoto, Tadamitsu
中科院分区：
文献类型：
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作者：
Hashimoto, Shigeru;Kishimoto, Tadamitsu
从 DNA 转录为 mRNA，然后从 mRNA 翻译为蛋白质的遗传信息受到复杂的转录后机制的调节。最近，人们已经清楚mRNA降解不仅可以去除不必要的mRNA，而且还与翻译起始的调节密切相关，对于维持细胞稳态至关重要。据报道，各种RNA结合蛋白（RBP）通过各种信号转导途径在mRNA稳定性和翻译起始机制中发挥核心作用，并通过响应细胞内和细胞外刺激的转录后修饰比转录过程更快地调节基因表达，而不需要从头合成蛋白质。另一方面，炎症对于消除与感染相关的病原体是必要的，并且受到严格控制以避免炎症细胞因子的过度表达，例如白介素6（IL-6）和肿瘤坏死因子（TNF）。人们越来越清楚，RBP 在这些免疫反应的转录后调节中发挥着重要作用。此外，研究表明，RBP 的异常调节会导致慢性炎症和自身免疫性疾病。尽管自19世纪鲁道夫·维尔肖(Rudolf Virchow)时代以来人们就认识到癌症相关炎症会导致肿瘤的发生和进展，但在癌症恶性转化中，免疫监视系统的抗肿瘤免疫与癌症相关炎症的促肿瘤免疫之间的平衡被破坏仍然难以捉摸。最近，参与促炎细胞因子产生调节的代表性 RBP 的表达和激活失调已被证明与肿瘤进展有关。在这篇综述中，我们总结了最近在了解这些 RBP 在几种类型的免疫反应中的功能作用以及 RBP 失调在免疫疾病和癌症发病机制中的作用方面取得的进展，并讨论了通过靶向 RBP 结合免疫疗法来治疗癌症的可能治疗策略。
Genetic information that is transcribed from DNA to mRNA, and then translated from mRNA to protein, is regulated by complex and sophisticated post-transcriptional mechanisms. Recently, it has become clear that mRNA degradation not only acts to remove unnecessary mRNA, but is also closely associated with the regulation of translation initiation, and is essential for maintaining cellular homeostasis. Various RNA-binding proteins (RBPs) have been reported to play central roles in the mechanisms of mRNA stability and translation initiation through various signal transduction pathways, and to modulate gene expression faster than the transcription process via post-transcriptional modifications in response to intracellular and extracellular stimuli, without de novo protein synthesis. On the other hand, inflammation is necessary for the elimination of pathogens associated with infection, and is tightly controlled to avoid the overexpression of inflammatory cytokines, such as inter-leukin 6 (IL-6) and tumor necrosis factor (TNF). It is increasingly becoming clear that RBPs play important roles in the post-transcriptional regulation of these immune responses. Furthermore, it has been shown that the aberrant regulation of RBPs leads to chronic inflammation and autoimmune diseases. Although it has been recognized since the time of Rudolf Virchow in the 19th century that cancer-associated inflammation contributes to tumor onset and progression, involvement of the disruption of the balance between anti-tumor immunity via the immune surveillance system and pro-tumor immunity by cancer-associated inflammation in the malignant transformation of cancer remains elusive. Recently, the dysregulated expression and activation of representative RBPs involved in regulation of the production of pro-inflammatory cytokines have been shown to be involved in tumor progression. In this review, we summarize the recent progress in our understanding of the functional roles of these RBPs in several types of immune responses, and the involvement of RBP dysregulation in the patho-genesis of immune diseases and cancer, and discuss possible therapeutic strategies against cancer by targeting RBPs, coupled with immunotherapy.