ZNF503 accelerates aggressiveness of hepatocellular carcinoma cells by down-regulation of GATA3 expression and regulated by microRNA-495

Am J Transl Res. 2019 Jun 15;11(6):3426-3437. eCollection 2019.

Abstract

Zinc finger protein ZNF503 is an important regulator during developmental process and tumor initiation. ZNF503 drives tumor development and process and was cancer-specific dysregulated in cancers. However, its expression and function in hepatocellular carcinoma (HCC) still need to be studied and elucidated. In this study, we demonstrated for the first time that ZNF503 mRNA and protein was up-regulated in HCC tissues and cell lines. Clinical data showed that high ZNF503 was significantly correlated with poor prognostic features, including advanced TNM stage and venous invasion. Moreover, ZNF503 was identified as a potential 5-year prognostic marker of HCC patients. Notably, ZNF503 promoted migration, invasion and EMT progress. ZNF503 was recruited to GATA3 promoter and inhibited its expression. GATA3 inhibited HCC cells migration, invasion and EMT process. Furthermore, we demonstrated that ZNF503 expression was regulated by miR-495. In HCC tissues. MiR-495 has an inverse correlation with ZNF503 expression. Conclusively, our data revealed that ZNF503 promoted migration, invasion and EMT process through regulating GATA3 expression, which was regulated by miR-495, suggesting the potential therapeutic value for HCC.

Keywords: EMT; GATA3; ZNF503; hepatocellular carcinoma; miR-495.