Cao Ziyu, Li Yingrui
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.
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.
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.
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。