Relationship between changes in the exon-recognition machinery and SLC22A1 alternative splicing in hepatocellular carcinoma

Publication date: Available online 15 January 2020Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Meraris Soto, Maria Reviejo, Ruba Al-Abdulla, Marta R. Romero, Rocio I.R. Macias, Loreto Boix, Jordi Bruix, Maria A. Serrano, Jose J.G. MarinAbstractChanges 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 ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research

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