Abstract:
Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality. Human phenylalanine tRNA synthetase (PheRS) comprises two α catalytic subunits encoded by the FARSA gene and two β regulatory subunits encoded by the FARSB gene. FARSB is a potential oncogene, but no experimental data show the relationship between FARSB and HCC progression. We found that the high expression of FARSB in liver cancer is closely related to patients\' low survival and poor prognosis. In liver cancer cells, the mRNA and protein expression levels of FARSB are increased and promote cell proliferation and migration. Mechanistically, FARSB activates the mTOR complex 1 (mTORC1) signaling pathway by binding to the component Raptor of the mTORC1 complex to play a role in promoting cancer. In addition, we found that FARSB can inhibit erastin-induced ferroptosis by regulating the mTOR signaling pathway, which may be another mechanism by which FARSB promotes HCC progression. In summary, FARSB promotes HCC progression and is associated with the poor prognosis of patients. FARSB is expected to be a biomarker for early screening and treatment of HCC.
摘要:
肝细胞癌(HCC)是一种常见的恶性肿瘤,死亡率高。人苯丙氨酸tRNA合成酶(PheRS)包含由FARSA基因编码的两个α催化亚基和由FARSB基因编码的两个β调节亚基。FARSB是一种潜在的癌基因,但没有实验数据显示FARSB与HCC进展之间的关系。我们发现FARSB在肝癌中的高表达与患者的低生存率和不良预后密切相关。在肝癌细胞中,FARSBmRNA和蛋白表达水平升高,促进细胞增殖和迁移。机械上,FARSB通过与mTORC1复合物的Raptor结合来激活mTOR复合物1(mTORC1)信号通路,从而在促进癌症中发挥作用。此外,我们发现FARSB可以通过调节mTOR信号通路来抑制擦除素诱导的铁细胞凋亡,这可能是FARSB促进HCC进展的另一种机制。总之,FARSB促进HCC进展,并与患者的不良预后相关。FARSB有望成为HCC早期筛查和治疗的生物标志物。