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Increased expression of G9A contributes to carcinogenesis and indicates poor prognosis in hepatocellular carcinoma

机译:G9A表达增加有助于癌变并预示肝细胞癌预后不良

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摘要

Euchromatic histone-lysine N-methyltransferase (G9A), the primary histone methyltransferase for histone H3 Lys9, has been identified to be upregulated in numerous types of cancer. The aim of the present study was to analyze the clinical significance of G9A, and preliminarily explore its function in hepatocellular carcinoma (HCC). An increased expression level of G9A was demonstrated in the HCC samples and also in 5 publically available datasets. By analyzing , it was revealed that its expression level was significantly associated with serum α-fetoprotein level of patients with HCC, and may serve as a potential prognostic indicator for patients with multinodular HCC. Bioinformatics tools were utilized to predict the potential function of G9A, and the results indicated that G9A may modulate gene sets involved in RNA processing and DNA replication. G9A inhibition may suppress cell proliferation by arresting cells in G1 phase and increasing the expression level of microtubule-associated protein light chain 3β (MAP1LC3B) in Huh7 and HepG2 cells. In addition, an inverse association between the expression of G9A and LC3B was demonstrated in HCC tumor samples in the publically available dataset, which indicated that G9A may also have the potential to regulate MAP1LC3B expression in HCC tumor tissues. The results of the present study led to hypothesis that the G9A expression level may be of assistance in diagnosing HCC, and be a potential therapeutic target for HCC. The results provided novel evidence for additional understanding of the crucial role of G9A in tumorigenesis.
机译:正常的组蛋白赖氨酸N-甲基转移酶(G9A)是组蛋白H3 Lys 9 的主要组蛋白甲基转移酶,已被发现在多种类型的癌症中均被上调。本研究的目的是分析G9A的临床意义,并初步探讨其在肝细胞癌(HCC)中的功能。在HCC样本和5个公开可用的数据集中证明了G9A的表达水平增加。通过分析,发现其表达水平与肝癌患者血清α-甲胎蛋白水平显着相关,并可作为多结节性肝癌患者的潜在预后指标。利用生物信息学工具预测了G9A的潜在功能,结果表明G9A可以调节参与RNA加工和DNA复制的基因集。 G9A抑制可通过将细胞停在G1期并增加Huh7和HepG2细胞中微管相关蛋白轻链3β(MAP1LC3B)的表达水平来抑制细胞增殖。此外,在可公开获得的数据集中的HCC肿瘤样本中,G9A和LC3B的表达呈负相关,这表明G9A也可能具有调节HCC肿瘤组织中MAP1LC3B表达的潜力。本研究的结果得出这样的假设,即G9A表达水平可能有助于诊断HCC,并且可能是HCC的潜在治疗靶标。结果为进一步了解G9A在肿瘤发生中的关键作用提供了新的证据。

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