Browsing by Author "Caiado, Helena Isabel Rosa Pinto"
Now showing 1 - 1 of 1
Results Per Page
Sort Options
- Molecular basis for the epigenetic regulation of MGP in cancerPublication . Caiado, Helena Isabel Rosa Pinto; Cancela, Leonor; Conceição, NatérciaMatrix Gla protein (MGP) is a member of the vitamin K-dependent family of proteins and a known physiological inhibitor of ectopic calcifications. Mutations in its gene cause Keutel syndrome, a rare autosomal recessive disorder characterized by severe soft tissue calcification. Despite its involvement in multiple calcifying pathologies, MGP has been described as playing a potential role in carcinogenesis, thus contributing to trigger interest in this gene towards exploring its potential as a cancer prognostic factor. These findings lead us to the main objective of this work which consisted of the study of the MGP gene in different types of tumors, to identify possible epigenetic patterns and transcriptional regulators responsible for controlling MGP gene expression in cancer. In this sense, we analyzed the expression pattern of MGP at mRNA and protein levels in a variety of tumors, initially using tissue biopsies from colorectal patients, and then exploring, through bioinformatics analysis, the data available in The Cancer Genome Atlas and The Human Protein Atlas. Results demonstrated a correlation between high levels of MGP with advanced stages of cancer progression and poor overall survival outcome, establishing MGP as an independent prognostic factor for the patient’s overall survival We also evaluated the methylation status in four of the six CpG sites, located in the MGP promoter region (cg13302154; cg22221831, and cg00431549) and first intron (cg0560958), between healthy and tumoral tissue. Results showed a correlation between MGP mRNA expression and the different methylation patterns across all the analyzed tumors, providing evidence for epigenetic regulation of MGP transcription. Moreover, we investigated several putative transcriptional regulators through transient transfections with luciferase reporter assays, demonstrating that YY1, GATA1, and C/EBPα are negative regulators of the MGP promoter. Altogether, our data contribute to provide novel insights on MGP regulation, strengthening the hypothesis that MGP plays a role during cancer progression/proliferation.