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MODELLING THE IMPACT OF OXIDATIVE STRESS AND INFLAMMATION IN MELANOMA USING THE ZEBRAFISH
Autores:
SOFÍA IBAÑEZ MOLERO
,
ELENA GOMEZ ABENZA
,
FRANCISCO JAVIER MARTÍNEZ MORCILLO
,
DIANA GARCIA MORENO
,
VICTORIANO MULERO MÉNDEZ
,
Grupos de investigación:
[GI/IMIB/C060/2011] Inmunidad, inflamación y cáncer
[GI/IMIB/C003/2011] Cirugía digestiva, endocrina y trasplante de órganos abdominales
Comunicación:
Antecedentes:
It has been previously described that there is a close relationship between oxidative stress, inflammation and cancer progression. In this crosstalk, DUOX1-derived H2O2 has been shown to play a critical role. In addition, both the gpx3 and alox5 genes have been found to be involved in this process and have recently emerged as interesting targets for cancer treatment.
Métodos:
We have used GEO and PronogScan databases to analyse gene expression in melanoma patients. To understand the role of DUOX1-derived H2O2 in melanoma aggressiveness, we have generated a transgenic zebrafish with tissue-restricted expression of a dominant negative form of Duox1. Using a zebrafish melanoma model and CRISPR-Cas9 genome editing, we will also generate tissue-specific gene mutants to shed light into the roles of these genes in melanoma progression.
Resultados:
Using GEO and PronogScan databases, we found that DUOX1 gene expression declined during melanoma progression, while high expression was associated to good prognosis of melanoma patients. Furthermore, we have found gpx3 and alox5 to be highly expressed in a zebrafish model of melanoma with skin chronic inflammation. Interestingly, high expression of both genes has been found to be associated to good prognosis of melanoma patients.
Conclusiones:
In conclusion, DUOX1, gpx3 and alox5 genes are associated with good prognosis of melanoma patients, revealing the importance of oxidative stress in melanoma progression. Future experiments with zebrafish transgenic lines will be useful to better understand this process.
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