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

// Bijun Qiu 1, * , Junqi Wang 2, * , Yingxue Yu 1, 3, * , Chao Zhen 2 , Jinyang Gu 1 , Wenjun Liu 3 , Yankai Wen 1, 3 , Lili Chen 1, 3 , Yueqiu Gao 2 , Qiang Xia 1 , Xiaoni Kong 1 1 Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China 2 Department of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China 3 School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China * B.Q, J.W and Y.Y contributed equally to this work Correspondence to: Xiaoni Kong, email: xiaoni-kong@126.com Qiang Xia, email: xiaqiang@medmail.com.cn Yueqiu Gao, email: gaoyueqiu@hotmail.com. Keywords: DJ-1, IL-6/STAT3, hepatocellular carcinoma, MHCC-97L Received: September 20, 2016     Accepted: December 01, 2016     Published: December 27, 2016 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.