Identifying UBA2 as a proliferation and cell cycle regulator in lung cancer A549 cells
Identifying UBA2 as a proliferation and cell cycle regulator in lung cancer A549 cells
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DOI：
10.1002/jcb.28543
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发表时间：
2019-08-01
影响因子：
4
通讯作者：
Fan, Chuifeng
中科院分区：
文献类型：
--
作者：
Jiang, Biying;Fan, Xiaoxi;Fan, Chuifeng
泛素活化酶2(UBA2)是苏木糖基化系统中E1活化酶的基本组成部分。UBA2在人类肿瘤中的表达和功能目前尚不清楚。本研究探讨UBA2在人非小细胞肺癌中的表达及其作用。免疫组织化学结果显示UBA2在肺癌组织中高表达(53.3%，40/75)，高于正常肺组织(14.3%，4/28)(P<；0.05)。UBA2免疫染色主要定位于胞核。UBA2在癌组织中的过度表达与肿瘤分化程度低、肿瘤体积大(>；5.0 cm)、T分期高(T3+4)、淋巴结转移和TNM分期晚期(III+IV)显著相关。体外研究表明，UBA2在A549、95D、H1975和H1299细胞中均有表达。UBA2基因在A549细胞中的表达显著抑制了癌细胞的增殖，上调了癌细胞的凋亡率(P<；0.05)。细胞周期分析显示，UBA_2基因敲除后，A549细胞的G1、G2/M期细胞明显增多，S期细胞明显减少(P<；0.05)。在A549细胞中，UBA2基因被敲除后的基因表达谱显示，与细胞周期、细胞死亡和存活以及细胞生长和增殖关系最密切的功能。Western印迹分析显示，UBA2基因敲除可显著抑制多聚ADP-核糖聚合酶1、小染色体维持7(MCM7)、MCM2、MCM3和MCM7的表达。这些结果表明，UBA2是一种重要的细胞周期和增殖调节因子，可能是一种新的肿瘤标志物。
Ubiquitin activating enzyme 2 (UBA2) is a basic component of E1-activating enzyme in the SUMOylation system. Expression and function of UBA2 in human cancers are largely unknown. In this study we investigate UBA2 expression the function in human non-small-cell lung cancer. Immunochemistry study showed that UBA2 was overexpressed in cancer tissues (53.3%, 40 of 75) compared with normal lung tissues (14.3%, 4 of 28) (P < 0.05). Immunostaining of UBA2 was mainly detected in nucleus. Overexpression of UBA2 in cancer tissues was significantly associated with poor differentiation, large tumor size ( > 5.0 cm), higher T stages (T3 + 4), lymph node metastasis and advanced TNM stages (III + IV). In vitro study showed that UBA2 was expressed in A549, 95D, H1975, and H1299 cells. Knockdown of UBA2 in A549 cells significantly inhibited cancer cell proliferation and upregulated cancer cell apoptosis (P < 0.05). Cell cycle analysis showed that knockdown of UBA2 in A549 cell significantly increased the G1 and G2/M phase cells and reduced the S phase cells (P < 0.05). Gene expression profile after knockdown of UBA2 in A549 cells showed that the most related function was cell cycle, cell death and survival, and cellular growth and proliferation. Western blot analysis study showed that knockdown of UBA2 significantly inhibited expression of poly(ADP-ribose) polymerase 1, mini-chromosome maintenance 7 (MCM7), MCM2, MCM3 and MCM7. These results indicated that UBA2 was a critical cell cycle and proliferation regulator and may be a novel cancer marker in this malignant tumor.