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Updated: Sep 23, 2025
Evaluation of Exon Inclusion Induced by Splice Switching Antisense Oligonucleotides in SMA Patient Fibroblasts
Published on: May 11, 2018
Inhibition of the expression of oncogene SRSF3 by blocking an exonic splicing suppressor with antisense
Jihua Guo1,2, Xiaoxuan Che1, Xiaole Wang1
1Hubei-MOST KLOS & KLOBME, School & Hospital of Stomatology, Wuhan University 237 Luoyu Road Wuhan 430079 PR China jiarong@whu.edu.cn +86 87686268.
Abstract:
Antisense oligonucleotides (ASOs) have been widely used to regulate alternative splicing of pre-mRNA by targeting splice sites, branch points, or exonic splice enhancers to increase exon skipping or intron retention. So far, few studies have used ASOs to block exonic splicing suppressor (ESS) and increase exon inclusion. Previously, we demonstrated that serine and arginine rich splicing factor 3 (SRSF3) (also called SRp20) is an oncogene. The inclusion of its alternative exon 4 down-regulates its expression. An ESS motif is responsible for the skipping of alternative exon 4. Here, we used an economical method to screen effective anti-ESS ASO. We discovered that an ASO targeting the ESS motif can promote the inclusion of exon 4, reduce SRSF3 expression, and inhibit cell growth in oral cancer cells. Our results suggested that using anti-ESS ASOs can efficiently increase exon inclusion and be used as a potential anti-cancer drug.
Insights
Antisense oligonucleotides (ASOs) targeting exonic splicing suppressors (ESS) can increase exon inclusion. This approach reduces oncogene SRSF3 expression and inhibits oral cancer cell growth, showing potential as an anti-cancer therapy.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- Antisense oligonucleotides (ASOs) are utilized to modulate pre-mRNA alternative splicing.
- Few studies have explored ASOs for blocking exonic splicing suppressors (ESS) to enhance exon inclusion.
- Serine and arginine rich splicing factor 3 (SRSF3) is an oncogene, with exon 4 inclusion down-regulating its expression.
Purpose of the Study:
- To develop an economical method for screening effective anti-ESS ASOs.
- To investigate the potential of ASOs in promoting exon inclusion by targeting ESS motifs.
- To evaluate the therapeutic potential of anti-ESS ASOs in oral cancer.
Main Methods:
- Screening of effective anti-ESS ASOs using an economical method.
- Treatment of oral cancer cells with identified ASOs targeting the ESS motif.
- Assessment of exon 4 inclusion, SRSF3 expression levels, and cell proliferation.
Main Results:
- An ASO targeting the ESS motif effectively promoted exon 4 inclusion.
- SRSF3 expression was reduced in oral cancer cells treated with the ASO.
- ASO treatment inhibited cell growth in oral cancer cells.
Conclusions:
- Targeting ESS motifs with ASOs is an efficient strategy to increase exon inclusion.
- Anti-ESS ASOs demonstrate potential as a novel anti-cancer therapeutic approach for oral cancer.
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