High Expression of UPK3A Promotes the Progression of Gastric Cancer Cells by Inactivating p53 Pathway.

IF 2.6 4区医学 Q3 CELL BIOLOGY

Analytical Cellular Pathology Pub Date : 2022-06-21 eCollection Date: 2022-01-01 DOI:10.1155/2022/6897561

Deliang Xu, Jing Guo, Hongwei Xu

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Abstract

Background: Gastric cancer is a common gastrointestinal tract cancer and is a considerable health burden worldwide. TCGA analysis found Uroplakin 3A (UPK3A) was upregulated in gastric cancer tissues. Our study was designed to investigate the underlying mechanism of Uroplakin 3A (UPK3A) in gastric cancer.

Methods: Data from TCGA database were used to assess the expression, and Kaplan-Meier plotter analysis was used to assess the prognosis value of UPK3A. Furthermore, there are effects of UPK3A silencing on the activity, proliferation, migration, and invasion of human gastric cancer cells (SNU-216 and HGC-27) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, wound healing, and Transwell assays. In addition, the expression of UPK3A, p53, KLF4, ZMAT3, MDM2, and SP1 was detected by qRT-PCR and Western blot assay.

Results: UPK3A was markedly upregulated in gastric cancer tissues compared to that in normal tissues, and patients with high UPK3A level showed poor prognosis. UPK3A was highly expressed in human gastric cancer cell lines compared to that in a normal human gastric epithelial cell line. Silencing of UPK3A inhibited the proliferation, migration, and invasion of gastric cancer cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that UPK3A was involved in the p53 signaling pathway. UPK3A suppressed the activation of p53 signaling pathway, and treatment with Pifithrin-α (an inhibitor of the p53 signaling pathway) or silencing of p53 significantly reversed the effect of UPK3A silencing on the expression of p53, KLF4, ZMAT3, MDM2, and SP1.

Conclusion: Our findings showed that UPK3A promotes the progression of gastric cancer by regulating the p53 signaling pathway and could be a potential therapeutic target for gastric cancer.

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UPK3A高表达通过灭活p53通路促进胃癌细胞的进展。

背景:胃癌是一种常见的胃肠道肿瘤，是世界范围内相当大的健康负担。TCGA分析发现，Uroplakin 3A (UPK3A)在胃癌组织中表达上调。我们的研究旨在探讨Uroplakin 3A (UPK3A)在胃癌中的潜在机制。方法:采用TCGA数据库数据评估UPK3A的表达，采用Kaplan-Meier绘图图分析评估UPK3A的预后价值。此外，通过3-(4,5-二甲基噻唑-2-酰基)-2,5-二苯基溴化四唑(MTT)、菌落形成、伤口愈合和Transwell实验，研究了UPK3A沉默对人胃癌细胞(SNU-216和HGC-27)的活性、增殖、迁移和侵袭的影响。此外，采用qRT-PCR和Western blot检测UPK3A、p53、KLF4、ZMAT3、MDM2、SP1的表达。结果:UPK3A在胃癌组织中较正常组织明显上调，UPK3A高表达的患者预后较差。UPK3A在人胃癌细胞系中高表达，而在正常人胃上皮细胞系中高表达。UPK3A的沉默抑制了胃癌细胞的增殖、迁移和侵袭。京都基因与基因组百科(KEGG)通路富集分析显示，UPK3A参与p53信号通路。UPK3A抑制p53信号通路的激活，用聚氟乙烯酯-α (p53信号通路抑制剂)或沉默p53可显著逆转UPK3A沉默对p53、KLF4、ZMAT3、MDM2和SP1表达的影响。结论:我们的研究结果表明，UPK3A通过调节p53信号通路促进胃癌的进展，可能是胃癌的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Analytical Cellular Pathology ONCOLOGY-CELL BIOLOGY

CiteScore

4.90

自引率

3.10%

发文量

审稿时长

16 weeks

期刊介绍： Analytical Cellular Pathology is a peer-reviewed, Open Access journal that provides a forum for scientists, medical practitioners and pathologists working in the area of cellular pathology. The journal publishes original research articles, review articles, and clinical studies related to cytology, carcinogenesis, cell receptors, biomarkers, diagnostic pathology, immunopathology, and hematology.