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Updated: Jul 27, 2025
Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
How Driver Oncogenes Shape and Are Shaped by Alternative Splicing Mechanisms in Tumors
Weronika Wojtyś1, Magdalena Oroń1
1Laboratory of Human Disease Multiomics, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland.
Abstract:
The development of RNA sequencing methods has allowed us to study and better understand the landscape of aberrant pre-mRNA splicing in tumors. Altered splicing patterns are observed in many different tumors and affect all hallmarks of cancer: growth signal independence, avoidance of apoptosis, unlimited proliferation, invasiveness, angiogenesis, and metabolism. In this review, we focus on the interplay between driver oncogenes and alternative splicing in cancer. On one hand, oncogenic proteins-mutant p53, CMYC, KRAS, or PI3K-modify the alternative splicing landscape by regulating expression, phosphorylation, and interaction of splicing factors with spliceosome components. Some splicing factors-SRSF1 and hnRNPA1-are also driver oncogenes. At the same time, aberrant splicing activates key oncogenes and oncogenic pathways: p53 oncogenic isoforms, the RAS-RAF-MAPK pathway, the PI3K-mTOR pathway, the EGF and FGF receptor families, and SRSF1 splicing factor. The ultimate goal of cancer research is a better diagnosis and treatment of cancer patients. In the final part of this review, we discuss present therapeutic opportunities and possible directions of further studies aiming to design therapies targeting alternative splicing mechanisms in the context of driver oncogenes.
Insights
Aberrant pre-messenger RNA splicing is altered in tumors, impacting cancer hallmarks. Driver oncogenes and splicing factors interact, influencing cancer development and offering potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- RNA sequencing advances enable study of aberrant pre-messenger RNA splicing in tumors.
- Altered splicing patterns are prevalent across cancers, affecting key cancer hallmarks.
- This review explores the intricate relationship between driver oncogenes and alternative splicing in cancer.
Purpose of the Study:
- To review the interplay between driver oncogenes and alternative splicing in cancer.
- To highlight how oncogenic proteins influence splicing patterns.
- To discuss how aberrant splicing activates oncogenic pathways and potential therapeutic strategies.
Main Methods:
- Literature review focusing on RNA sequencing, cancer hallmarks, driver oncogenes, and alternative splicing.
- Analysis of molecular mechanisms linking oncogenes to splicing factor regulation.
- Examination of oncogenic pathways activated by aberrant splicing.
Main Results:
- Driver oncogenes (mutant p53, CMYC, KRAS, PI3K) modulate splicing by regulating splicing factors.
- Some splicing factors (SRSF1, hnRNPA1) function as driver oncogenes.
- Aberrant splicing reactivates critical oncogenes and pathways (p53 isoforms, RAS-RAF-MAPK, PI3K-mTOR).
Conclusions:
- The interplay between driver oncogenes and alternative splicing is central to cancer development.
- Targeting alternative splicing mechanisms presents a promising therapeutic avenue for cancer treatment.
- Further research is needed to develop effective therapies focused on splicing alterations in the context of driver oncogenes.
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