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.