肝细胞癌组织O-GlcNAc糖基化水平变化及其与血管生成素2表达的关系
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摘要
目的探讨肝细胞癌组织O-N-乙酰葡萄糖胺(O-GlcNAc)糖基化水平变化及其与血管生成素2(Ang2)表达的关系。方法选择肝细胞癌患者57例(观察组)、肝脏良性占位性病变患者40例(对照组),取手术切除的肝细胞癌组织及肝脏良性占位性病变组织,采用RT-PCR法和Western blotting法检测O-GlcNAc糖苷水解酶(OGA)、O-GlcNAc糖基转移酶(OGT)、Ang2 mRNA和蛋白表达。结果观察组OGA、OGT、Ang2 mRNA和蛋白表达均明显高于对照组(P均<0.05);相关分析显示,OGA、OGT表达与Ang2表达均呈正相关关系(P均<0.05);肝细胞癌组织OGA、OGT、Ang2蛋白表达均与BCLC分期有关,OGT、Ang2蛋白表达还与淋巴结转移有关(P均<0.05)。结论肝细胞癌组织O-GlcNAc糖基化水平明显升高;O-GlcNAc糖基化有可能通过调节Ang2表达促进肝细胞癌的发生、发展。
引文
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[3] Xu Z,Isaji T,Fukuda T,et al.O-GlcNAcylation regulates integrin-mediated cell adhesion and migrationvia formation of focal adhesion complexes[J].J Biol Chem,2019,249(9):3117-3124.
[4] Arivazhagan J,Nandeesha H,Dorairajan LN,et al.Association of elevated interleukin-17 and angiopoietin-2 with prostate size in benign prostatic hyperplasia[J].Aging Male,2017,20(2):115-118.
[5] Chen Y,Wu Y,Zhang X,et al.Angiopoietin-2 (Ang-2) is a useful serum tumor marker for liver cancer in the Chinese population[J].Clin Chim Acta,2018,478:18-27.
[6] Xu W,Zhang X,Wu JL,et al.O-GlcNAc transferase promotes fatty liver-associated liver cancer through inducing palmitic acid and activating endoplasmic reticulum stress[J].J Hepatol,2017,67(2):310-320.
[7] Qiao Y,Zhang X,Zhang Y,et al.High glucose stimulates tumorigenesis in hepatocellular carcinoma cells through AGER-dependent O-GlcNAcylation of c-Jun[J].Diabetes,2016,65(3):619-632.
[8] Azuma Y,Miura K,Higai K,et al.Protein O-N-acetylglucosaminylation modulates promoter activities of cyclic AMP response element and activator protein 1 and enhances E-selectin expression on HuH-7 human hepatoma cells[J].Biol Pharm Bull,2007,30(12):2284-2289.
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[13] Yao D,Taguchi T,Matsumura T,et al.High glucose increases angiopoietin-2 transcription in microvascular endothelial cells through methylglyoxal modification of mSin3A[J].J Biol Chem,2007,282(42):31038-31045.