Upregulation of Enzymes involved in ISGylation and Ubiquitination in patients with hepatocellular carcinoma
Upregulation of Enzymes involved in ISGylation and Ubiquitination in patients with hepatocellular carcinoma
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DOI：
10.7150/ijms.39823
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发表时间：
2020-01-01
影响因子：
3.6
通讯作者：
Nguyen Linh Toan
中科院分区：
文献类型：
--
作者：
Hoang Van Tong;Nghiem Xuan Hoan;Nguyen Linh Toan
背景：ISG化是ISG15与靶蛋白的偶联反应。ISG化通过酶的级联反应发生，这与泛素化类似。通过ISG化，ISG15可以与参与细胞增殖和分化的蛋白质结合，从而促进恶性肿瘤的发生和发展。方法：采用实时荧光定量聚合酶链式反应技术检测38对肝细胞癌患者癌组织及癌旁组织中参与ISG化过程的相关基因(EFP、HERC5、UbA1、UbC和USP18)的基因表达，并与临床实验室指标进行相关分析。结果：肿瘤组织中EFP、HERC5、UbA1和USP18mRNA的相对表达水平显著高于癌旁组织(P=0.006；0.012；0.02%和0.039)。肿瘤组织中基因表达的相关模式不同于癌旁组织的相关模式。癌旁组织中EFP、HERC5和UBA1的相对表达与直接胆红素水平呈正相关(Spearman‘s Rho分别为0.31、0.33和0.45，P分别为0.06、0.05和0.01)，USP18的相对表达与ALT水平呈负相关(Spearman’s Rho=-0.33，P=0.03)。结论：EFP、HERC5、UBA1和USP18基因在肝癌组织中表达上调，可能与肝细胞癌的发生有关。
Background: ISGylation is the conjugation of ISG15 with target proteins. ISGylation occurs through an enzymatic cascade, which is similar to that of ubiquitination. Through ISGylation, ISG15 can bind to proteins involved in cell proliferation and differentiation, thus promoting genesis and progression of malignancies. The present study aims to investigate expression of genes involved in ISGylation and ubiquitination in patients with hepatocellular carcinoma and to correlate gene expression with clinical laboratory parameters of these patients.Methods: mRNA expression of genes encoding enzymes involved in the ISGylation process (EFP, HERC5, UBA1, UBC and USP18) was evaluated by quantitative real-time PCR in 38 pairs of tumour and adjacent non-tumour tissues from patients with hepatocellular carcinoma and correlated with distinct clinical laboratory parameters.Results: Relative mRNA expression of EFP, HERC5, UBA1 and USP18 was significantly higher in tumour tissues compared to adjacent non-tumour tissues (P=0.006; 0.012; 0.02 and 0.039, respectively). The correlation pattern of mRNA expression between genes in the tumours differed from the pattern in adjacent non-tumour tissues. Relative expression of EFP, HERC5 and UBA1 in adjacent non-tumour tissues was positively associated with direct bilirubin levels (Spearman's rho=0.31, 0.33 and 0.45; P=0.06, 0.05 and 0.01, respectively) and relative expression of USP18 in adjacent non-tumour tissues correlated negatively with ALT levels (Spearman's rho=-0.33, P=0.03).Conclusions: EFP, HERC5, UBA1, and USP18 genes are upregulated in tumour tissues of patients with HCC and, thus, may be associated with the pathogenesis of hepatocellular carcinoma.