三阴性乳腺癌(triple-negative breast cancer,TNBC)是一种侵袭性极强且预后不良的乳腺癌亚型.RNA选择性剪接异常在TNBC的发生和发展中发挥关键作用.本文系统介绍RNA剪接的基本过程,重点综述TNBC中的异常选择性剪接事件及其生物学效应:1)多个剪接相关因子通过调控细胞存活和药物反应相关基因的选择性剪接,促进肿瘤细胞增殖并介导化疗耐药;2)剪接调控网络的紊乱可引起多个转移相关基因的剪接改变,促进肿瘤侵袭转移;3)异常的选择性剪接事件通过影响DNA损伤修复基因的表达参与肿瘤进展;4)选择性剪接的失调还参与调控肿瘤免疫逃逸和干细胞特性.深入理解RNA选择性剪接失调在TNBC中的作用机制,对于阐明其分子病理基础、发现新的预后标志物和制订治疗策略具有重要意义.
Mechanisms of RNA alternative splicing dysregulation in triple-negative breast cancer
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.
triple-negative breast canceralternative splicingsplicing factorstumorigenesisinvasion and metastasisDNA damage repairprognostic biomarkerstherapeutic targets
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