Publicação
Alternative Splicing of EXOC7 in Colorectal Cancer Development
| Resumo: | Colorectal cancer (CRC) is the third most frequent cancer and the fourth most lethal in the world. Recently, switches in specific alternative splicing (AS) events in cancer-associated genes, have been correlated with the acquisition of proliferative advantage for cells. Thus, using the public repository of The Cancer Genome Atlas (TCGA), the group of Nuno Barbosa-Morais at iMM have identified a signature of 46 AS events that significantly correlated with overall survival of colorectal cancer (CRC) patients, independent of gene expression. They found that inclusion of part of exon 8 from the EXOC7 gene (expression of isoform 5 rather than isoform 2) is one of these 46 AS events with a high prognostic value in CRC. EXOC7 is a key component of the exocyst complex and plays an important role in several cellular processes such as migration. Furthermore, differential expression of EXOC7 isoforms had already been correlated with breast tumour progression. In this project, we aim to validate the prognostic value of EXOC7 isoforms in a cohort of human CRC samples and explore its biological role in vitro. Overall, our results showed that levels of expression of EXOC7 isoform 5 are a good prognostic marker in CRC, independent of EXOC7 total expression. However, cellular overexpression of isoform 5 and 2 do not seem to affect biological processes such as exocytosis, epithelial-to-mesenchymal transition (EMT), or cytoskeleton organization. Finally, we believe that our study has allowed the validation of a good prognostic marker in CRC, not only, important in the identification of patients most likely to progress, but also, revealing a potential target of therapy. Nevertheless, more studies are needed in order to unravel the biological role of EXOC7 isoforms in vitro. |
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| Autores principais: | Ramalho, Daniela Maria Grou |
| Assunto: | Colorectal cancer exocyst EXOC7 isoform 5 prognostic value splicing events |
| Ano: | 2018 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| Resumo: | Colorectal cancer (CRC) is the third most frequent cancer and the fourth most lethal in the world. Recently, switches in specific alternative splicing (AS) events in cancer-associated genes, have been correlated with the acquisition of proliferative advantage for cells. Thus, using the public repository of The Cancer Genome Atlas (TCGA), the group of Nuno Barbosa-Morais at iMM have identified a signature of 46 AS events that significantly correlated with overall survival of colorectal cancer (CRC) patients, independent of gene expression. They found that inclusion of part of exon 8 from the EXOC7 gene (expression of isoform 5 rather than isoform 2) is one of these 46 AS events with a high prognostic value in CRC. EXOC7 is a key component of the exocyst complex and plays an important role in several cellular processes such as migration. Furthermore, differential expression of EXOC7 isoforms had already been correlated with breast tumour progression. In this project, we aim to validate the prognostic value of EXOC7 isoforms in a cohort of human CRC samples and explore its biological role in vitro. Overall, our results showed that levels of expression of EXOC7 isoform 5 are a good prognostic marker in CRC, independent of EXOC7 total expression. However, cellular overexpression of isoform 5 and 2 do not seem to affect biological processes such as exocytosis, epithelial-to-mesenchymal transition (EMT), or cytoskeleton organization. Finally, we believe that our study has allowed the validation of a good prognostic marker in CRC, not only, important in the identification of patients most likely to progress, but also, revealing a potential target of therapy. Nevertheless, more studies are needed in order to unravel the biological role of EXOC7 isoforms in vitro. |
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