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Updated: Aug 11, 2025

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
Non-canonical functions of spliceosome components in cancer progression
Olga M Ivanova1,2,3, Ksenia S Anufrieva4,5, Anastasia N Kazakova5,6
1Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, 119435, Russian Federation. sci.olga.ivanova@gmail.com.
Abstract:
Dysregulation of pre-mRNA splicing is a common hallmark of cancer cells and it is associated with altered expression, localization, and mutations of the components of the splicing machinery. In the last few years, it has been elucidated that spliceosome components can also influence cellular processes in a splicing-independent manner. Here, we analyze open source data to understand the effect of the knockdown of splicing factors in human cells on the expression and splicing of genes relevant to cell proliferation, migration, cell cycle regulation, DNA repair, and cell death. We supplement this information with a comprehensive literature review of non-canonical functions of splicing factors linked to cancer progression. We also specifically discuss the involvement of splicing factors in intercellular communication and known autoregulatory mechanisms in restoring their levels in cells. Finally, we discuss strategies to target components of the spliceosome machinery that are promising for anticancer therapy. Altogether, this review greatly expands understanding of the role of spliceosome proteins in cancer progression.
Insights
Dysregulation of pre-mRNA splicing factors impacts cancer progression through both splicing-dependent and independent mechanisms. Targeting spliceosome components offers promising anticancer therapeutic strategies.
Area of Science:
- Molecular Biology
- Cancer Biology
- Genetics
Background:
- Dysregulation of pre-messenger RNA (pre-mRNA) splicing is a hallmark of cancer.
- Splicing machinery components are frequently altered in cancer cells.
- Emerging evidence shows spliceosome components influence cellular processes independently of splicing.
Purpose of the Study:
- To analyze the impact of splicing factor knockdown on genes related to cancer hallmarks.
- To review non-canonical functions of splicing factors in cancer progression.
- To explore spliceosome-targeted anticancer therapies.
Main Methods:
- Analysis of open-source data on splicing factor knockdown in human cells.
- Literature review of splicing factors' roles in cancer progression and intercellular communication.
- Discussion of autoregulatory mechanisms and therapeutic targeting strategies.
Main Results:
- Splicing factor knockdown affects expression and splicing of genes involved in proliferation, migration, cell cycle, DNA repair, and cell death.
- Splicing factors exhibit non-canonical functions crucial for cancer progression.
- Intercellular communication and autoregulation play roles in spliceosome component homeostasis.
Conclusions:
- Spliceosome proteins are critical regulators in cancer, acting through both canonical and non-canonical pathways.
- Understanding these roles is vital for developing novel anticancer therapies.
- Targeting spliceosome components presents a promising avenue for cancer treatment.
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