MicroRNA485-3p negatively regulates the transcriptional co-repressor CtBP1 to control the oncogenic process in osteosarcoma cells

Carboxyl-terminal binding protein 1 ( ), a well-known transcriptional co-repressor, is highly expressed in a number of cancer types. However, it is still absent in osteosarcoma cells. Here, we found that , but not , is overexpressed in invasive osteosarcoma tissues and cells. The overexpressed in turn represses its downstream targets, such as the pro-apoptotic regulators , and p53 upregulated modulator of apoptosis ( ), cell adhesion molecule , and the cell cycle regulators , and phosphatase and tensin homolog ( ). To explore the molecular mechanism of overexpression, we subjected three independent clinical samples to miRNA microarray analysis and found that miR-485-3p could specifically bind to the 3'-untranslated region (3'-UTR) of , thereby negatively controlling expression. The overexpression of miR-485-3p in osteosarcoma cells significantly repressed levels and inhibited cell proliferation, colony formation, cell migration and sphere formation. Further analysis indicated that DNA hypermethylation in the promoter region of miR-485-3p caused the downregulation of miR-485-3p. Treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine (AZA) resulted in the upregulation of miR-485-3p and the downregulation of as well as inhibited osteosarcoma cell growth. This study provides evidence that is also overexpressed in osteosarcoma cells and demonstrates the underlying mechanism regarding its overexpression. Thus, therapeutically targeting CtBP1 may represent an effective strategy for osteosarcoma therapy.