摘要
可变剪接(alternative splicing)是人类基因表达调节的关键途径,它在扩大功能蛋白的多样性方面起着决定性作用。可变剪接事件是肿瘤进展中的一个重要生物标志物,它与肿瘤的发展密切相关。肿瘤细胞倾向于产生有利于其进展的可变剪接体,因此,针对肿瘤特异性可变剪接体进行靶向调控是肿瘤治疗的一个潜在策略。在此,本文对可变剪接和肿瘤之间的复杂关系做了一个简要回顾。可变剪接通过去除前体mRNA(pre-mRNA)的非编码序列,并将蛋白质编码片段以不同的组合方式进行组装,最终产生具有不同甚至相反功能的蛋白质。可变剪接事件可以通过凋亡、侵袭和转移、血管生成和代谢,促进正常细胞向肿瘤细胞的转变;也可通过影响免疫通路中起关键作用的基因,从而影响癌症治疗的有效性。通过直接或间接靶向可变剪接因子以及基于寡核苷酸的疗法是目前逆转肿瘤可变剪接事件的主要策略。这些发现将有助于研究者更好地了解与肿瘤相关的可变剪接,并为肿瘤的治疗开发新的策略。
Alternative splicing is the key to human gene expression regulation and plays a decisive role in enlarging the diversity of functional proteins.Alternative splicing is an important biomarker in tumor progression,which is closely related to the development of tumors.Tumor cells tend to produce alternative spliceosome that are conducive to their progression.Therefore,targeting regulation of tumor-specific alternative spliceosomes is a potential strategy for tumor therapy.Herein,we provide a brief review of the complex relationship between alternative splicing and tumors.Alternative splicing works by removing non-coding sequences of pre-mRNA and assembling protein-coding fragments in different combinations,ultimately producing proteins with different or even opposite functions.Alternative splicing events can promote the transformation of tumor cells through apoptosis,invasion,metastasis,angiogenesis,and metabolism;they can also influence the effectiveness of cancer immunotherapy by affecting genes that play a key role in the immune pathway.We proposed that direct or indirect targeting of alternative splicing factors and oligonucleotide-based therapies are the main strategies to reverse tumor alternative splicing events.These findings will help us to better understand tumor-related alternative splicing and to develop new strategies for tumor treatment.
作者
于海洋
李自祥
刘博
YU Hai-yang;LI Zi-xiang;LIU Bo(State Key Laboratory of Component-based Chinese Medicine,Institute of Traditional Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;State Key Laboratory of Biotherapy and Cancer Center,Sichuan University,Chengdu 610041,China)
出处
《药学学报》
CAS
CSCD
北大核心
2023年第8期2098-2110,共13页
Acta Pharmaceutica Sinica
基金
国家重点研发计划(2021YFE0203100)
现代中医药海河实验室科技项目(HH2022X1008).
