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Updated: Jun 3, 2025

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
Mechanisms of RNA alternative splicing dysregulation in triple-negative breast cancer
Ziyu Cao1,2, Yingrui Li3
1Zhejiang University-University of Edinburgh Institute, Haining Zhejiang 314400, China. ziyuc.21@intl.zju.edu.cn.
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.
Insights
RNA alternative splicing dysregulation drives aggressive triple-negative breast cancer (TNBC) progression. Understanding these aberrant splicing events is key to developing new TNBC treatments and prognostic markers.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with a poor prognosis.
- RNA alternative splicing is a crucial post-transcriptional process often dysregulated in cancer.
Purpose of the Study:
- To review the role of aberrant RNA alternative splicing in TNBC initiation and progression.
- To highlight the biological effects of splicing dysregulation on TNBC characteristics.
Main Methods:
- Systematic review of RNA splicing processes.
- Analysis of aberrant alternative splicing events in TNBC.
- Review of literature on splicing factors and their targets in TNBC.
Main Results:
- Splicing factor dysregulation promotes TNBC cell proliferation and chemotherapy resistance.
- Altered splicing of metastasis-related genes facilitates tumor invasion and metastasis.
- Aberrant splicing impacts DNA damage repair, immune evasion, and stem cell properties in TNBC.
Conclusions:
- RNA alternative splicing dysregulation is a significant driver of TNBC.
- Targeting splicing mechanisms offers potential for novel TNBC prognostic markers and therapeutic strategies.
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