The miR-124-Prolyl Hydroxylase P4HA1-MMP1 axis plays a critical role in prostate cancer progression

摘要: Collagen prolyl hydroxylases (C-P4HAs) are a family of enzymes involved in collagen biogenesis. One the isoforms P4HA, Prolyl 4-hydroxylase, alpha polypeptide I (P4HA1), catalyzes formation 4-hydroxyproline that is essential for proper three-dimensional folding newly synthesized procollagen chains. Here, we show overexpression P4HA1 aggressive prostate cancer. Immunohistochemical analysis using tissue microarray demonstrated expression was correlated with cancer progression. Using vitro studies, showed plays critical role cell growth and tumor Expression profiling studies P4HA1-modulated cells suggested regulation Matrix metalloprotease 1. The invasive properties overexpressing were reversed by blocking MMP1. Our indicate copy number gain subset metastatic tumors its also regulated microRNA-124. MiR-124 turn negatively transcriptional repressors EZH2 CtBP1, both which overexpressed Chick chorioallantoic membrane (CAM) assay mice xenograft investigations required metastasis vivo. observations suggest progression could serve as viable therapeutic target.