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PRPF8与癌症关系的研究进展

Research Progress on the Relationship Between PRPF8 and Cancer.

作者信息

Huang Guoqing, Wang Dandan, Xue Jiaying

机构信息

Institute of Advanced Technology, Heilongjiang Academy of Sciences, Harbin 150001, China.

出版信息

Curr Issues Mol Biol. 2025 Feb 26;47(3):150. doi: 10.3390/cimb47030150.

DOI:10.3390/cimb47030150
PMID:40136404
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11941625/
Abstract

Alternative splicing (AS) plays a crucial role in regulating gene expression and protein diversity, influencing both normal cellular function and pathological conditions, including cancer. Protein pre-mRNA processing factor 8 (PRPF8), a core component of the spliceosome, is integral to the splicing process, ensuring accurate gene transcription and spliceosome assembly. Disruptions in PRPF8 function are linked to a variety of cancers, as mutations in this gene can induce abnormal splicing events that contribute to tumorigenesis, metastasis, and drug resistance. This review provides an in-depth analysis of the mechanisms by which PRPF8 regulates tumorigenesis through AS, exploring its role in diverse cancer types, including breast, liver, myeloid, and colorectal cancers. Furthermore, we examine the molecular pathways associated with PRPF8 dysregulation and their impact on cancer progression. We also discuss the emerging potential of targeting PRPF8 in cancer therapy, highlighting challenges in drug development.

摘要

可变剪接(Alternative splicing,AS)在调节基因表达和蛋白质多样性方面发挥着关键作用,影响正常细胞功能和包括癌症在内的病理状况。蛋白质前体mRNA加工因子8(PRPF8)是剪接体的核心组成部分,对剪接过程至关重要,可确保准确的基因转录和剪接体组装。PRPF8功能的破坏与多种癌症相关,因为该基因的突变可诱导异常剪接事件,从而促进肿瘤发生、转移和耐药性。本综述深入分析了PRPF8通过可变剪接调节肿瘤发生的机制,探讨其在多种癌症类型中的作用,包括乳腺癌、肝癌、髓系癌和结直肠癌。此外,我们研究了与PRPF8失调相关的分子途径及其对癌症进展的影响。我们还讨论了在癌症治疗中靶向PRPF8的新兴潜力,强调了药物开发中的挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/425b/11941625/300e648f0473/cimb-47-00150-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/425b/11941625/300e648f0473/cimb-47-00150-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/425b/11941625/300e648f0473/cimb-47-00150-g001.jpg

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本文引用的文献

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LncRNA ZNF649-AS1 promotes trastuzumab resistance and TAM-dependent PD-L1 expression in breast cancer by regulating EXOC7 alternative splicing.长链非编码 RNA ZNF649-AS1 通过调控 EXOC7 的可变剪接促进乳腺癌对曲妥珠单抗的耐药性和 TAM 依赖性 PD-L1 的表达。
Arch Biochem Biophys. 2024 Nov;761:110128. doi: 10.1016/j.abb.2024.110128. Epub 2024 Aug 17.
2
Spliceosomic dysregulation in pancreatic cancer uncovers splicing factors PRPF8 and RBMX as novel candidate actionable targets.胰腺癌中的剪接体失调揭示了剪接因子 PRPF8 和 RBMX 作为新的潜在可操作靶标。
Mol Oncol. 2024 Oct;18(10):2524-2540. doi: 10.1002/1878-0261.13658. Epub 2024 May 24.
3
PRPF8-mediated dysregulation of hBrr2 helicase disrupts human spliceosome kinetics and 5´-splice-site selection causing tissue-specific defects.
PRPF8 介导的 hBrr2 解旋酶失调破坏了人类剪接体动力学和 5´-剪接位点选择,导致组织特异性缺陷。
Nat Commun. 2024 Apr 11;15(1):3138. doi: 10.1038/s41467-024-47253-0.
4
Splicing inhibition mediated by reduced splicing factors and helicases is associated with the cellular response of lung cancer cells to cisplatin.由剪接因子和解旋酶减少介导的剪接抑制与肺癌细胞对顺铂的细胞反应相关。
Comput Struct Biotechnol J. 2023 Dec 28;23:648-658. doi: 10.1016/j.csbj.2023.12.039. eCollection 2024 Dec.
5
Altered splicing machinery in lung carcinoids unveils NOVA1, PRPF8 and SRSF10 as novel candidates to understand tumor biology and expand biomarker discovery.肺类癌中的剪接机制改变揭示了 NOVA1、PRPF8 和 SRSF10 作为新的候选物,以了解肿瘤生物学并扩大生物标志物的发现。
J Transl Med. 2023 Dec 4;21(1):879. doi: 10.1186/s12967-023-04754-8.
6
The function of alternative splicing in the proteome: rewiring protein interactomes to put old functions into new contexts.可变剪接在蛋白质组中的作用:重新连接蛋白质相互作用组,将旧功能置于新环境中。
Nat Struct Mol Biol. 2023 Dec;30(12):1844-1856. doi: 10.1038/s41594-023-01155-9. Epub 2023 Nov 30.
7
Genetic Control of Alternative Splicing and its Distinct Role in Colorectal Cancer Mechanisms.可变剪接的遗传控制及其在结直肠癌机制中的独特作用。
Gastroenterology. 2023 Nov;165(5):1151-1167. doi: 10.1053/j.gastro.2023.07.019. Epub 2023 Aug 3.
8
PRPF8 controls alternative splicing of PIRH2 to modulate the p53 pathway and survival of human ESCs.PRPF8 控制 PIRH2 的可变剪接,从而调节人 ESC 的 p53 通路和存活。
J Cell Physiol. 2023 Aug;238(8):1909-1920. doi: 10.1002/jcp.31066. Epub 2023 Jun 25.
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Intermediate Uveitis in Retinitis Pigmentosa Associated with a Novel Homozygous Splice Site Mutation in .色素性视网膜炎相关性中间葡萄膜炎与. 的新型纯合剪接位点突变相关。
Middle East Afr J Ophthalmol. 2022 Nov 23;29(1):59-62. doi: 10.4103/meajo.meajo_98_22. eCollection 2022 Jan-Mar.
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RNA splicing dysregulation and the hallmarks of cancer.RNA 剪接失调与癌症的特征。
Nat Rev Cancer. 2023 Mar;23(3):135-155. doi: 10.1038/s41568-022-00541-7. Epub 2023 Jan 10.