Unravelling the role of ACOX3 and MCT2 in prostate cancer

• Autor(a) principal: Oliveira, Rui Pedro Duarte
• Data de Publicação: 2018
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/25169
• topic: ACOX3; MCT2; Prostate cancer; Metabolism; β-oxidation

Prostate cancer has a high incidence rate in men, having a great impact on their life quality, being frequently the cause of death. It is a disease which presents challenges in terms of diagnostics and there is still no permanent and effective treatment. Prostate cancer, contrarily to the majority of other tumours, uses branched chain fatty acids as its main energy source in its initial stages. Recently, our group has reported that a protein involved in the metabolism of glucose, MCT2, is overexpressed in prostate cancer and that its presence at the peroxisomes leads to an increase in the β-oxidation of branched chain fatty acids. The goals of this work were to develop two 22Rv1 stable cell lines, one with the ACOX3 gene knocked out and the other with the MCT2 gene knocked out, using the CRISPR-Cas9 system. Additionally, in order to study the role of ACOX3 in prostate cancer, we created a N-terminal Myc-tagged ACOX3 construct. After several attempts, it was not possible to create the stable cell lines. Regarding the overexpression of ACOX3, no differences were observed in the peroxisome’s dynamics, as well as in the proliferation of 22Rv1 cells. The specific role of peroxisomes, namely through the action of ACOX3 and MCT2, in prostate cancer development still requires further research. The CRISPR-Cas9 system remains an interesting tool for these studies, but a refinement of its protocol is necessary in order to achieve a higher efficiency in the future