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阴阳-1的上调与食管癌的增殖和谷氨酰胺代谢相关。

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

作者信息

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

机构信息

Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000 Sichuan, China.

Translational Medicine Research Center, North Sichuan Medical College, Nanchong, 637000 Sichuan, China.

出版信息

Int J Genomics. 2022 Mar 20;2022:9305081. doi: 10.1155/2022/9305081. eCollection 2022.

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.

摘要

目的

探讨阴阳1(YY1)在食管癌(ESCA)中的表达及其对ESCA谷氨酰胺代谢的影响。

方法

使用一系列生物信息学数据库和工具研究YY1在ESCA中的表达及作用。采用实时PCR、蛋白质印迹法和免疫组织化学染色法验证ESCA组织与相应癌旁组织中YY1的表达。此外,检测YY1对食管鳞癌细胞增殖和迁移的影响。通过蛋白质印迹法评估YY1与谷氨酰胺代谢之间的相关性。

结果

YY1基因在进化过程中高度保守,在ESCA组织和食管鳞癌细胞系(ECA109和TE-1)中上调。此外,YY1可能影响免疫细胞浸润水平并促进肿瘤细胞免疫逃逸。功能富集分析发现YY1参与许多生物学过程,如细胞分裂以及谷胱甘肽和谷氨酰胺代谢。在ECA109和TE-1中用小干扰RNA敲低YY1后,ECA109和TE-1的增殖和迁移受到抑制。谷氨酰胺消耗和谷氨酸生成显著减少。丙氨酸-、丝氨酸-、半胱氨酸偏好转运体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,可能促进食管鳞癌细胞的谷氨酰胺代谢,表明其可能作为ESCA的诊断生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f6/8961439/482154d6aaab/IJG2022-9305081.001.jpg

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