Down-regulation of argininosuccinate lyase induces hepatoma cell apoptosis through activating Bax signaling pathway

Rui Gong; Lin He; HongZhong Zhou; ShengTao Cheng; Fang Ren; Juan Chen; JiHua Ren

doi:10.1016/j.gendis.2018.11.003

Down-regulation of argininosuccinate lyase induces hepatoma cell apoptosis through activating Bax signaling pathway

Genes Dis. 2018 Nov 28;6(3):296-303. doi: 10.1016/j.gendis.2018.11.003. eCollection 2019 Sep.

Authors

Rui Gong¹, Lin He¹, HongZhong Zhou¹, ShengTao Cheng¹, Fang Ren¹, Juan Chen¹, JiHua Ren¹

Affiliation

¹ The Key Laboratory of Molecular Biology of Infectious Diseases Designated by the Chinese Ministry of Education, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.

Abstract

Argininosuccinate lyase (ASL) plays an important role in the hepatic urea cycle, and can catalyze the reversible reaction of argininosuccinate to arginine and fumarate. However, the function of ASL in hepatocellular carcinoma (HCC) is not fully understood. In this study, we found that ASL expression was frequently upregulated in HCC tissues and HCC cell lines. Knock down of ASL inhibited cell proliferation and induced apoptosis in HCC cells. Mechanistic studies revealed the BCL2-associated X protein (Bax) signaling pathway which determines cancer cell apoptosis was regulated by ASL. Moreover, the depletion of Bax restored the inhibition of cell growth and reduced apoptosis initiated by ASL silencing. Together, the study demonstrated that ASL regulated HCC cell growth and apoptosis by modulating Bax signaling. Thus, the therapeutic targeting of ASL may offer options for HCC treatment.

Keywords: ASL; Apoptosis; Bax; HCC; Proliferation.