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RNA结合蛋白在胃肠道恶性肿瘤肿瘤免疫微环境中的调控作用

The regulatory roles of RNA-binding proteins in the tumour immune microenvironment of gastrointestinal malignancies.

作者信息

Li Dongqi, Chu Xiangyu, Liu Weikang, Ma Yongsu, Tian Xiaodong, Yang Yinmo

机构信息

Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, Beijing, China.

Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

出版信息

RNA Biol. 2025 Dec;22(1):1-14. doi: 10.1080/15476286.2024.2440683. Epub 2024 Dec 24.

Abstract

The crosstalk between the tumour immune microenvironment (TIME) and tumour cells promote immune evasion and resistance to immunotherapy in gastrointestinal (GI) tumours. Post-transcriptional regulation of genes is pivotal to GI tumours progression, and RNA-binding proteins (RBPs) serve as key regulators via their RNA-binding domains. RBPs may exhibit either anti-tumour or pro-tumour functions by influencing the TIME through the modulation of mRNAs and non-coding RNAs expression, as well as post-transcriptional modifications, primarily N6-methyladenosine (mA). Aberrant regulation of RBPs, such as HuR and YBX1, typically enhances tumour immune escape and impacts prognosis of GI tumour patients. Further, while targeting RBPs offers a promising strategy for improving immunotherapy in GI cancers, the mechanisms by which RBPs regulate the TIME in these tumours remain poorly understood, and the therapeutic application is still in its early stages. This review summarizes current advances in exploring the roles of RBPs in regulating genes expression and their effect on the TIME of GI tumours, then providing theoretical insights for RBP-targeted cancer therapies.

摘要

肿瘤免疫微环境(TIME)与肿瘤细胞之间的相互作用促进了胃肠道(GI)肿瘤的免疫逃逸和对免疫治疗的抵抗。基因的转录后调控对胃肠道肿瘤的进展至关重要,而RNA结合蛋白(RBPs)通过其RNA结合结构域发挥关键调节作用。RBPs可能通过调节mRNA和非编码RNA的表达以及转录后修饰(主要是N6-甲基腺苷(mA))来影响TIME,从而表现出抗肿瘤或促肿瘤功能。RBPs的异常调节,如HuR和YBX1,通常会增强肿瘤免疫逃逸并影响胃肠道肿瘤患者的预后。此外,虽然靶向RBPs为改善胃肠道癌症的免疫治疗提供了一种有前景的策略,但RBPs在这些肿瘤中调节TIME的机制仍知之甚少,其治疗应用仍处于早期阶段。本综述总结了探索RBPs在调节基因表达中的作用及其对胃肠道肿瘤TIME的影响的当前进展,进而为以RBPs为靶点的癌症治疗提供理论见解。

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