DJ-1 promotes development of DEN-induced hepatocellular carcinoma and proliferation of liver cancer cells

Abstract

Chronic liver inflammation and injuries play a critical role in development of hepatocellular carcinoma (HCC). Parkinson disease (autosomal recessive, early onset) 7, encoding PARK7 protein (also called DJ-1), plays important roles in many carcinogenesis processes and is essential in modulating inflammation. However, whether DJ-1 is involved in HCC development remains largely unknown. To determine the effect of DJ-1 on HCC development, we accessed the correlation of hepatic DJ-1 expression with overall survival (OS) and TNM stage in 96 HCC patients and found a significant inverse correlation between DJ-1 expression and OS. By adopting a classic diethylnitrosamine (DEN)-induced murine HCC model, DJ-1 knockout (KO) mice displayed reduced tumorigenesis and cell proliferation, accompanied by decreased hepatic inflammation and IL-6/STAT3 activation. Furthermore, after an acute DEN challenge, DJ-1 KO mice showed significant decreases in liver injury, hepatocyte proliferation and DNA damage. In a human HCC cell line (MHCC-97L), cancer cell proliferation was induced by overexpression of DJ-1 and is related to oncogenic signaling of MAPKs and AKT. Induction of DJ-1 may serve as a novel regulator for HCC cell proliferation and HCC development possibly through enhanced MAPK signaling and inflammation.