Abstract
Background
Endothelial progenitor cells (EPCs) play an important role in tumor angiogenesis and growth. In this study, we assessed the effect of MicroRNAs (miRNAs) on EPCs migration and angiogenesis and its signaling pathway in patients suffered from ovarian cancer (OC).
Methods
We cultured peripheral circulating EPCs derived from 32 OC patients and 20 healthy control subjects, respectively. The miRNA profiles of EPCs in ovarian cancer patients were compared with that in healthy control subjects, and aberrantly expressed miRNAs in both groups were identified via miRNA microarray and clustering analysis. Among these miRNAs, miR-133a-5p was considered as one of the most important miRNAs, which biological function in EPCs has been investigated. Bioinformatic analysis combined with knockdown and overexpression of miR-133a-5p were used to identify its target protein.
Results
An obviously downregulated expression level of miR-133a-5p has been seen in EPCs with ovarian cancer patients. Downregulated expression level of miR-133a-5p has been seen in ovarian cancer tissues and ovarian cancer cells (SKOV-3 and OVCAR-3). Downregulated of miR-133a-5p can increase TRIM59 expression, moreover, downregulated of miR-133a-5p further induce migration and angiogenesis via increase VEGF and Id1 in EPCs. MiR-133a-5p pro-angiogenesis would be diminished by TRIM59 knockdown.
Conclusions
The study found that miR-133a-5p was an important upstream factor regulated Id1/VEGF expression. Additionally, functional studies have revealed that TRIM59 was a direct target protein of miR-133a-5p, and TRIM59 silencing attenuated the role of miR-133a-5p in angiogenesis and Id1/VEGF expression. So we proposed that miR-133a-5p would be a new target for OC therapy.
Dynamics of circulating endothelial cells and endothelial progenitor cells in breast cancer patients receiving cytotoxic chemotherapy
