Upregulation of DPY30 promotes cell proliferation and predicts a poor prognosis in cholangiocarcinoma
Upregulation of DPY30 promotes cell proliferation and predicts a poor prognosis in cholangiocarcinoma
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DPY30 的上调可促进细胞增殖并预测胆管癌的不良预后。
DOI：
10.1016/j.biopha.2019.109766
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发表时间：
2020-03-01
影响因子：
7.5
通讯作者：
Shen, Dong-Yan
中科院分区：
文献类型：
--
作者：
Hong, Zai-Fa;Zhang, Wen-Qing;Shen, Dong-Yan
目的：通过SET 1和MLL家族甲基转移酶复合物修饰赖氨酸4对组蛋白H3甲基化的影响与癌症进展密切相关。DPY 30是SET 1和MLL复合物的一个重要亚基，但其在胆管癌（cholangiocarcinoma，CCA）中的表达及其在肿瘤进展中的作用尚不清楚。用MTS法和集落形成法检测DPY 30基因敲低对CCA细胞增殖的影响，流式细胞仪分析细胞周期分布。结果：CCA组织中DPY 30 mRNA和蛋白水平均明显高于癌旁组织，且其上调与病理分化、肿瘤大小和TNM分期密切相关。Kaplan-Meier生存分析显示DPY 30表达上调与CCA患者的生存率显著相关，单因素和多因素分析显示DPY 30表达上调是CCA患者的独立预后因素。此外，DPY 30基因敲低还可抑制CCA细胞的体外生长，诱导细胞周期停滞在G2/M期，并减少糖酵解。结论：DPY 30上调可能促进CCA的发生，并与CCA患者的侵袭性恶性行为和不良生存结局有关。DPY 30可能成为治疗CCA患者的潜在新靶点。
Objectives: Modification of lysine 4 on histone H3 methylation by SET1 and MLL family methyltransferase complexes is tightly linked to cancer progression. DPY30 is an important subunit of SET1 and MLL complexes, however, its expression and roles in cancer progression was little known, especially in cholangiocarcinoma (CCA).Materials and Methods: The Q-PCR and IHC were performed to detect the levels of DPY30 mRNA and protein in CCA tissues. Effect of DPY30 knockdown on the proliferation of CCA cells was detected by MTS and colony formation, and cell cycle distribution was analyzed by flow cytometer. The glucose uptake, lactate release and ATP production assays were performed to detect the glycolysis of CCA cells.Results: The level of DPY30 mRNA and protein in CCA tissues were all significantly higher than that of peri-cancer tissues, and its upregulation was closely associated with pathological differentiation, tumor size, and TNM stage. In addition, Kaplan-Meier analysis of overall survival revealed that DPY30 upregulation was significantly associated with poor survival, and univariate and multivariate analysis indicated that it was an independently prognosis factor in CCA patients. Moreover, DPY30 knockdown inhibited in-vitro growth and induced cell cycle arrest at G2/M and decreased glycolysis in CCA cells.Conclusions: DPY30 upregulation may promote the development of CCA and was associated with the aggressive malignant behavior and poor survival outcome of CCA patients. DPY30 might serve as a potential novel target for treatment of CCA patients.