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MT1G serves as a tumor suppressor in hepatocellular carcinoma by interacting with p53
Oncogenesis ( IF 6.2 ) Pub Date : 2019-11-15 , DOI: 10.1038/s41389-019-0176-5
Yingchao Wang , Gaoxiong Wang , Xionghong Tan , Kun Ke , Bixing Zhao , Niangmei Cheng , Yuan Dang , Naishun Liao , Fei Wang , Xiaoyuan Zheng , Qin Li , Xiaolong Liu , Jingfeng Liu

Poor prognosis of hepatocellular carcinoma (HCC) patients is frequently associated with rapid tumor growth, recurrence and drug resistance. MT1G is a low-molecular weight protein with high affinity for zinc ions. In the present study, we investigated the expression of MT1G, analyzed clinical significance of MT1G, and we observed the effects of MT1G overexpression on proliferation and apoptosis of HCC cell lines in vitro and in vivo. Our results revealed that MT1G was significantly downregulated in tumor tissues, and could inhibit the proliferation as well as enhance the apoptosis of HCC cells. The mechanism study suggested that MT1G increased the stability of p53 by inhibiting the expression of its ubiquitination factor, MDM2. Furthermore, MT1G also could enhance the transcriptional activity of p53 through direct interacting with p53 and providing appropriate zinc ions to p53. The modulation of MT1G on p53 resulted in upregulation of p21 and Bax, which leads cell cycle arrest and apoptosis, respectively. Our in vivo assay further confirmed that MT1G could suppress HCC tumor growth in nude mice. Overall, this is the first report on the interaction between MT1G and p53, and adequately uncover a new HCC suppressor which might have therapeutic values by diminishing the aggressiveness of HCC cells.



中文翻译:

MT1G通过与p53相互作用在肝细胞癌中起抑癌作用

肝细胞癌(HCC)患者的预后不良通常与肿瘤的快速生长,复发和耐药有关。MT1G是一种对锌离子具有高亲和力的低分子量蛋白质。在本研究中,我们调查了MT1G的表达,分析了MT1G的临床意义,并观察了MT1G过表达对HCC细胞系体外和体内增殖和凋亡的影响。我们的结果表明,MT1G在肿瘤组织中显着下调,并且可以抑制肝癌细胞的增殖并增强其凋亡。机制研究表明,MT1G通过抑制泛素化因子MDM2的表达来提高p53的稳定性。此外,MT1G还可以通过与p53直接相互作用并向p53提供适当的锌离子来增强p53的转录活性。MT1G对p53的调节导致p21和Bax的上调,分别导致细胞周期停滞和凋亡。我们的体内测定进一步证实了MT1G可以抑制裸鼠中HCC肿瘤的生长。总体而言,这是有关MT1G与p53相互作用的第一份报道,并充分揭示了一种新的HCC抑制剂,该抑制剂可能通过降低HCC细胞的侵袭性而具有治疗价值。

更新日期:2019-11-15
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