Inhibition of the expression of oncogene SRSF3 by blocking an exonic splicing suppressor with antisense oligonucleotides

摘要

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.