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Updated: Dec 30, 2025

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
Published on: October 9, 2014
Relationship between changes in the exon-recognition machinery and SLC22A1 alternative splicing in hepatocellular
Meraris Soto1, Maria Reviejo1, Ruba Al-Abdulla1
1HEVEFARM Group, University of Salamanca, IBSAL, Salamanca, Spain.
Abstract:
Changes in the phenotype that characterizes cancer cells are partly due to altered processing of pre-mRNA by the spliceosome. We have previously reported that aberrant splicing plays an essential role in the impaired response of hepatocellular carcinoma (HCC) to sorafenib by reducing the expression of functional organic cation transporter type 1 (OCT1, gene SLC22A1) that constitutes the primary way for HCC cells to take up this and other drugs. The present study includes an in silico analysis of publicly available databases to investigate the relationship between alternative splicing of SLC22A1 pre-mRNA and the expression of genes involved in the exon-recognition machinery in HCC and adjacent non-tumor tissue. Using Taqman Low-Density Arrays, the findings were validated in 25 tumors that were resected without neoadjuvant chemotherapy. The results supported previous reports showing that there was a considerable degree of alternative splicing of SLC22A1 in adjacent non-tumor tissue, which was further increased in the tumor in a stage-unrelated manner. Splicing perturbation was associated with changes in the profile of proteins determining exon recognition. The results revealed the importance of using paired samples for splicing analysis in HCC and confirmed that aberrant splicing plays an essential role in the expression of functional OCT1. Changes in the exon recognition machinery may also affect the expression of other proteins in HCC. Moreover, these results pave the way to further investigations on the mechanistic bases of the relationship between the expression of spliceosome-associated genes and its repercussion on the appearance of alternative and aberrant splicing in HCC.
Insights
Aberrant splicing of SLC22A1 pre-mRNA increases in hepatocellular carcinoma (HCC), reducing functional organic cation transporter 1 (OCT1) expression. This highlights the role of splicing changes in cancer drug response.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- Aberrant pre-mRNA processing by the spliceosome influences cancer cell phenotypes.
- Hepatocellular carcinoma (HCC) exhibits impaired response to sorafenib due to reduced organic cation transporter 1 (OCT1) expression, linked to aberrant splicing of its gene (SLC22A1).
Purpose of the Study:
- To investigate the relationship between alternative splicing of SLC22A1 pre-mRNA and the expression of exon-recognition machinery genes in HCC.
- To validate findings using paired tumor and non-tumor tissues.
Main Methods:
- In silico analysis of public databases.
- Taqman Low-Density Arrays for validation in 25 resected HCC tumors.
- Analysis of paired tumor and adjacent non-tumor tissues.
Main Results:
- Significant alternative splicing of SLC22A1 was observed in non-tumor tissue, further increased in HCC tumors irrespective of stage.
- Splicing perturbations correlated with altered expression of proteins involved in exon recognition.
- Paired sample analysis confirmed aberrant splicing's role in functional OCT1 expression reduction in HCC.
Conclusions:
- Aberrant splicing of SLC22A1 is a key factor in reduced OCT1 expression in HCC.
- Changes in the exon-recognition machinery may impact other protein expressions in HCC.
- Further research into spliceosome-associated genes and aberrant splicing in HCC is warranted.
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