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Updated: Nov 26, 2025
Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
Splicing factors: Insights into their regulatory network in alternative splicing in cancer
Jun-Xian Du1, Gui-Qi Zhu2, Jia-Liang Cai2
1Department of General Surgery, Zhongshan Hospital, Fudan University & State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China.
Abstract:
More than 95% of all human genes are alternatively spliced after transcription, which enriches the diversity of proteins and regulates transcript and/or protein levels. The splicing isoforms produced from the same gene can manifest distinctly, even exerting opposite effects. Mounting evidence indicates that the alternative splicing (AS) mechanism is ubiquitous in various cancers and drives the generation and maintenance of various hallmarks of cancer, such as enhanced proliferation, inhibited apoptosis, invasion and metastasis, and angiogenesis. Splicing factors (SFs) play pivotal roles in the recognition of splice sites and the assembly of spliceosomes during AS. In this review, we mainly discuss the similarities and differences of SF domains, the details of SF function in AS, the effect of SF-driven pathological AS on different hallmarks of cancer, and the main drivers of SF expression level and subcellular localization. In addition, we briefly introduce the application prospects of targeted therapeutic strategies, including small-molecule inhibitors, siRNAs and splice-switching oligonucleotides (SSOs), from three perspectives (drivers, SFs and pathological AS). Finally, we share our insights into the potential direction of research on SF-centric AS-related regulatory networks.
Insights
Alternative splicing (AS) diversifies proteins and impacts cancer hallmarks. Splicing factors (SFs) drive pathological AS, offering therapeutic targets like small-molecule inhibitors and splice-switching oligonucleotides (SSOs).
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- Alternative splicing (AS) generates protein diversity and regulates gene expression.
- AS is crucial in cancer, contributing to hallmarks like proliferation, apoptosis evasion, invasion, metastasis, and angiogenesis.
- Splicing factors (SFs) are key regulators of AS.
Purpose of the Study:
- To review the role of SF domains and their functions in AS.
- To examine how SF-driven pathological AS contributes to cancer hallmarks.
- To explore therapeutic strategies targeting SFs and pathological AS.
Main Methods:
- Literature review focusing on SFs, AS, and cancer.
- Analysis of SF domain structures and functions.
- Discussion of cancer hallmarks influenced by AS.
- Overview of targeted therapeutic approaches.
Main Results:
- SFs exhibit diverse domains and functions in regulating AS.
- Pathological AS driven by SFs contributes to multiple cancer hallmarks.
- SF expression and localization are critical drivers of aberrant AS.
- Targeted therapies including small-molecule inhibitors, siRNAs, and SSOs show promise.
Conclusions:
- SFs are central to pathological AS in cancer.
- Understanding SF-centric regulatory networks is vital for developing novel cancer therapies.
- Targeting SFs and AS pathways offers a promising therapeutic avenue.
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