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三阴性乳腺癌中RNA可变剪接失调的机制

Mechanisms of RNA alternative splicing dysregulation in triple-negative breast cancer.

作者信息

Cao Ziyu, Li Yingrui

机构信息

Zhejiang University-University of Edinburgh Institute, Haining Zhejiang 314400, China.

College of Biomedical Sciences, Faculty of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom.

出版信息

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2024 Jul 28;49(7):1143-1154. doi: 10.11817/j.issn.1672-7347.2024.240434.

DOI:10.11817/j.issn.1672-7347.2024.240434
PMID:39788502
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11495985/
Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype with poor prognosis. RNA alternative splicing dysregulation plays a critical role in the initiation and progression of TNBC. This article systematically introduces the basic process of RNA splicing and then focuses on reviewing the aberrant alternative splicing events and their biological effects in TNBC: 1) Multiple splicing-related factors promote tumor cell proliferation and mediate chemotherapy resistance by regulating the alternative splicing of genes involved in cell survival and drug response; 2) dysregulation of splicing regulatory networks leads to altered splicing of multiple metastasis-related genes, promoting tumor invasion and metastasis; 3) aberrant alternative splicing events participate in tumor progression by affecting the expression of DNA damage repair genes; 4) dysregulation of alternative splicing is also involved in the regulation of tumor immune evasion and stem cell properties. A deeper understanding of the mechanisms underlying RNA alternative splicing dysregulation in TNBC is essential for elucidating its molecular pathology, identifying novel prognostic markers, and developing therapeutic strategies.

摘要

三阴性乳腺癌(TNBC)是一种侵袭性很强的乳腺癌亚型,预后较差。RNA可变剪接失调在TNBC的发生和发展中起关键作用。本文系统介绍了RNA剪接的基本过程,然后重点综述了TNBC中异常的可变剪接事件及其生物学效应:1)多种剪接相关因子通过调节参与细胞存活和药物反应的基因的可变剪接来促进肿瘤细胞增殖并介导化疗耐药性;2)剪接调控网络失调导致多个转移相关基因的剪接改变,促进肿瘤侵袭和转移;3)异常的可变剪接事件通过影响DNA损伤修复基因的表达参与肿瘤进展;4)可变剪接失调还参与肿瘤免疫逃逸和干细胞特性的调节。深入了解TNBC中RNA可变剪接失调的机制对于阐明其分子病理学、鉴定新的预后标志物以及制定治疗策略至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e7b/11495985/53fc6be1d2fa/ZhongNanDaXueXueBaoYiXueBan-49-7-1143-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e7b/11495985/53fc6be1d2fa/ZhongNanDaXueXueBaoYiXueBan-49-7-1143-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e7b/11495985/53fc6be1d2fa/ZhongNanDaXueXueBaoYiXueBan-49-7-1143-g001.jpg

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本文引用的文献

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Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer.转移性肝癌中不同异常可变剪接的分子靶点及机制
World J Clin Oncol. 2024 Apr 24;15(4):531-539. doi: 10.5306/wjco.v15.i4.531.
2
Development and validation of AI/ML derived splice-switching oligonucleotides.基于人工智能/机器学习的剪接寡核苷酸的开发和验证。
Mol Syst Biol. 2024 Jun;20(6):676-701. doi: 10.1038/s44320-024-00034-9. Epub 2024 Apr 25.
3
NRF2 activation by cysteine as a survival mechanism for triple-negative breast cancer cells.
半胱氨酸对 NRF2 的激活作用是三阴性乳腺癌细胞的一种生存机制。
Oncogene. 2024 May;43(22):1701-1713. doi: 10.1038/s41388-024-03025-0. Epub 2024 Apr 10.
4
SF3A2 promotes progression and cisplatin resistance in triple-negative breast cancer via alternative splicing of MKRN1.SF3A2 通过 MKRN1 的选择性剪接促进三阴性乳腺癌的进展和顺铂耐药性。
Sci Adv. 2024 Apr 5;10(14):eadj4009. doi: 10.1126/sciadv.adj4009. Epub 2024 Apr 3.
5
Activation of ERβ hijacks the splicing machinery to trigger R-loop formation in triple-negative breast cancer.雌激素受体β(ERβ)的激活劫持剪接机制,在三阴性乳腺癌中引发 R 环形成。
Proc Natl Acad Sci U S A. 2024 Mar 26;121(13):e2306814121. doi: 10.1073/pnas.2306814121. Epub 2024 Mar 21.
6
Interrogations of single-cell RNA splicing landscapes with SCASL define new cell identities with physiological relevance.单细胞 RNA 剪接景观的剖析通过 SCASL 定义了具有生理相关性的新细胞身份。
Nat Commun. 2024 Mar 9;15(1):2164. doi: 10.1038/s41467-024-46480-9.
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Acta Naturae. 2023 Oct-Dec;15(4):23-31. doi: 10.32607/actanaturae.26826.
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