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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
Deregulation of splicing factors and breast cancer development
Marco Silipo1, Hannah Gautrey1, Alison Tyson-Capper2
1Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Abstract:
It is well known that many genes implicated in the development and progression of breast cancer undergo aberrant alternative splicing events to produce proteins with pro-cancer properties. These changes in alternative splicing can arise from mutations or single-nucleotide polymorphisms (SNPs) within the DNA sequences of cancer-related genes, which can strongly affect the activity of splicing factors and influence the splice site choice. However, it is important to note that absence of mutations is not sufficient to prevent misleading choices in splice site selection. There is now increasing evidence to demonstrate that the expression profile of ten splicing factors (including SRs and hnRNPs) and eight RNA-binding proteins changes in breast cancer cells compared with normal cells. These modifications strongly influence the alternative splicing pattern of many cancer-related genes despite the absence of any detrimental mutations within their DNA sequences. Thus, a comprehensive assessment of the splicing factor status in breast cancer is important to provide insights into the mechanisms that lead to breast cancer development and metastasis. Whilst most studies focus on mutations that affect alternative splicing in cancer-related genes, this review focuses on splicing factors and RNA-binding proteins that are themselves deregulated in breast cancer and implicated in cancer-related alternative splicing events.
Insights
Aberrant alternative splicing in breast cancer is driven by altered expression of splicing factors, not just mutations. Understanding these changes is key to uncovering cancer development and metastasis mechanisms.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- Aberrant alternative splicing of genes is a hallmark of breast cancer, producing pro-cancer proteins.
- Mutations or SNPs in cancer genes can alter splicing factor activity and splice site selection.
- However, altered splicing can occur even without DNA mutations.
Purpose of the Study:
- To review the role of deregulated splicing factors and RNA-binding proteins in breast cancer.
- To highlight the influence of altered splicing factor expression on cancer-related gene splicing.
- To emphasize the importance of assessing splicing factor status in breast cancer.
Main Methods:
- Literature review focusing on splicing factors and RNA-binding proteins in breast cancer.
- Analysis of studies reporting changes in expression profiles of splicing factors and RNA-binding proteins.
- Examination of evidence linking these expression changes to alternative splicing events in cancer-related genes.
Main Results:
- Expression profiles of ten splicing factors (including SR proteins and hnRNPs) and eight RNA-binding proteins are altered in breast cancer cells.
- These expression changes significantly impact alternative splicing patterns of numerous cancer-related genes.
- Altered splicing occurs independently of detrimental mutations in the affected genes' DNA sequences.
Conclusions:
- Splicing factor deregulation is a critical mechanism in breast cancer development and progression.
- Focusing on splicing factors and RNA-binding proteins offers new insights beyond mutation-centric studies.
- Comprehensive assessment of splicing factor status is crucial for understanding breast cancer and metastasis.
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