RNA可变剪接机制及其在肿瘤治疗中的研究进展OA
Research progress of RNA alternative splicing mechanisms and their roles in cancer therapy
RNA可变剪接(alternative splicing,AS)是基因表达调控的关键机制,通过产生多种 mRNA剪接异构体,增加蛋白质的多样性,对细胞生理过程如增殖、代谢、凋亡等至关重要.在肿瘤治疗领域,可变剪接的研究进展显著,异常的可变剪接参与调控肿瘤发生、发展的多种生物学过程.研究表明,特定剪接因子的突变或表达变化在多种癌症中起关键作用,如SF3B1、SRSF2、U2AF1等.在此基础上,本文总结了针对可变剪接的肿瘤治疗新策略,包括抑制剪接体组分、反义寡核苷酸(ASO)疗法以及克服肿瘤耐药性和免疫逃逸的方法,这些策略通过调控剪接因子和修饰酶的活性,展现出克服传统化疗耐药问题和增强免疫治疗效果的潜力.本综述从可变剪接的调控机制、在肿瘤中的作用及其在肿瘤治疗中的新策略和应用前景出发,全面探讨可变剪接在肿瘤研究和治疗中的重要性.
Alternative splicing(AS),a critical mechanism in gene expression regulation,is essential for cellular physiological processes such as proliferation,metabolism,and apoptosis via generating diverse mRNA isoforms and expanding protein diversity.In the field of oncology,AS has been significantly implicated in the regulation of various biological processes involved in tumorigenesis and cancer progression.Specific mutations or expression changes in splicing factors,such as SF3B1,SRSF2,and U2AF1,play key roles in multiple types of cancer.This review summarizes novel therapeutic strategies for cancer targeting alternative splicing,including inhibiting spliceosome components,antisense oligonucleotide(ASO)therapy,and approaches to overcome drug resistance and immune evasion in cancer.These strategies,which modulate the activity of splicing factors and RNA-modifying enzymes,show promise in addressing chemoresistance and enhancing the efficacy of immunotherapy.This review provides a comprehensive exploration of alternative splicing mechanisms,their role in cancer,and their potential as a therapeutic target,highlighting the importance of alternative splicing in cancer research and therapy.
黄昕欣;唐铭珠;王多伟
中国药科大学基础医学与临床药学学院,南京 211198||中国药科大学转化医学研究院,南京 210009中国药科大学基础医学与临床药学学院,南京 211198||中国药科大学转化医学研究院,南京 210009中国药科大学基础医学与临床药学学院,南京 211198||中国药科大学转化医学研究院,南京 210009
医药卫生
可变剪接剪接体肿瘤治疗靶向药物反义寡核苷酸疗法耐药治疗
alternative splicingspliceosomecancer therapytargeted drugsantisense oligonucleotide therapydrug resistance therapy
《中国药科大学学报》 2026 (2)
155-162,8
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