Upregulation of Yin-Yang-1 Associates with Proliferation and Glutamine Metabolism in Esophageal Carcinoma

Can Luo, Xin Chen, Yuting Bai, Lei Xu, Shuqi Wang, Lihua Yao, Xiaolan Guo, Dongsheng Wang, Xiaowu Zhong
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Abstract

Objective. To investigate the expression of Yin-Yang-1 (YY1) in esophageal carcinoma (ESCA) and its effect on glutamine metabolism in ESCA. Methods. The expression and roles of YY1 in ESCA were investigated using a series of bioinformatics databases and tools. The expression of YY1 between ESCA tissues with the corresponding adjacent tissues was validated using real-time PCR, western blot, and immunohistochemical staining method. Furthermore, the effects of YY1 on ESCC cell proliferation and migration were examined. The correlation between the YY1 and glutamine metabolism was evaluated by western blot. Results. YY1 gene was highly conserved in evolution and upregulated in ESCA tissues and ESCC cell lines (ECA109 and TE-1). In addition, YY1 may affect the level of immune cell infiltration and promote tumor cell immune escape. Functional enrichment analysis found that YY1 involved in many biological processes, such as cell division and glutathione and glutamine metabolism. After siRNA knockdown of YY1 in ECA109 and TE-1, the proliferation and the migration of ECA109 and TE-1 were suppressed. The glutamine consumption and glutamate production were significantly decreased. The protein expression of alanine-, serine-, cysteine-preferring transporter 2 (ASCT2), glutaminase (GLS), and glutamate dehydrogenase (GLUD1) was significantly downregulated. Conclusion. YY1 is highly expressed in ESCA and may promote glutamine metabolism of ESCC cells, indicating it may be as a diagnostic biomarker for ESCA.

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食管癌组织中阴阳-1表达上调与细胞增殖及谷氨酰胺代谢相关
目的探讨阴阳-1 (YY1)在食管癌组织中的表达及其对谷氨酰胺代谢的影响。方法利用一系列生物信息学数据库和工具研究YY1在ESCA中的表达及其作用。采用real-time PCR、western blot、免疫组化染色等方法验证YY1在ESCA组织与相应相邻组织间的表达。进一步观察YY1对ESCC细胞增殖和迁移的影响。western blot检测YY1与谷氨酰胺代谢的相关性。结果YY1基因在ESCA组织和ESCC细胞系(ECA109和TE-1)中高度保守,在进化过程中表达上调。此外,YY1可能影响免疫细胞浸润水平,促进肿瘤细胞免疫逃逸。功能富集分析发现,YY1参与许多生物过程,如细胞分裂和谷胱甘肽和谷氨酰胺代谢。在ECA109和TE-1中siRNA敲除YY1后,ECA109和TE-1的增殖和迁移受到抑制。谷氨酰胺消耗量和谷氨酸产量显著降低。丙氨酸、丝氨酸、半胱氨酸偏好转运蛋白2 (ASCT2)、谷氨酰胺酶(GLS)和谷氨酸脱氢酶(GLUD1)的蛋白表达显著下调。结论YY1在ESCA中高表达,可促进ESCC细胞谷氨酰胺代谢,可作为ESCA的诊断标志物。
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Comparative and Functional Genomics
Comparative and Functional Genomics 生物-生化与分子生物学
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