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

机译:精氨酸琥珀酸裂合酶的下调通过激活Bax信号通路诱导肝癌细胞凋亡

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摘要

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.
机译:精氨酸琥珀酸裂合酶(ASL)在肝素尿素循环中起着重要的作用,并且可以催化精氨酸琥珀酸与精氨酸和富马酸酯的可逆反应。但是,尚不完全了解ASL在肝细胞癌(HCC)中的功能。在这项研究中,我们发现ASL表达在HCC组织和HCC细胞系中经常被上调。抑制ASL抑制HCC细胞增殖并诱导其凋亡。机理研究表明,决定癌细胞凋亡的BCL2相关X蛋白(Bax)信号通路受ASL调节。此外,Bax的消耗恢复了对细胞生长的抑制,并减少了ASL沉默引发的凋亡。总之,该研究表明ASL通过调节Bax信号传导来调节HCC细胞的生长和凋亡。因此,ASL的治疗靶点可能为HCC治疗提供选择。

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