TRIM28通过Wnt/β-catenin信号通路抑制胃癌细胞的癌干样特征。

IF 2.8 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Experimental Biology and Medicine Pub Date : 2023-12-01 Epub Date: 2023-12-06 DOI:10.1177/15353702231211970
Tingting Ning, Mengran Zhao, Nan Zhang, Zhaoqing Wang, Shutian Zhang, Mo Liu, Shengtao Zhu
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引用次数: 0

摘要

TRIM28对胃肿瘤发生的影响及其可能的分子机制有待进一步研究。我们旨在探索TRIM28在胃癌(GC)中的重要作用并揭示其潜在的分子机制。通过免疫组化分析20对胃癌及瘤周组织,测定TRIM28的表达水平。我们采用了多种检测方法来探讨TRIM28在GC中的重要作用。采用Western blotting和qRT-PCR分析TRIM28与Wnt/β-catenin信号通路的关系。TRIM28在胃癌组织中的表达高于瘤周组织。TRIM28在胃癌中的高表达与良好的预后效果相关。体外功能实验表明,敲除TRIM28可促进GC细胞的增殖和克隆形成。此外,敲低TRIM28可提高GC细胞干性标志物的表达水平,增强GC细胞的成球性和耐药特性,提示对GC细胞干性有重要影响。此外,我们的分析表明,Wnt/β-catenin信号通路参与了TRIM28对GC细胞干性的影响,阻断Wnt/β-catenin信号通路明显挽救了TRIM28敲低的促进作用。综上所述,TRIM28通过Wnt/β-catenin信号通路调节GC细胞的茎样特性具有重要影响,提示TRIM28是一个有前景的药物靶点和潜在的预后预测因子。
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TRIM28 suppresses cancer stem-like characteristics in gastric cancer cells through Wnt/β-catenin signaling pathways.

The influences of TRIM28 on the gastric tumorigenesis together with potential molecular mechanisms remain to be studied. We aimed at exploring the important effects of TRIM28 on gastric cancer (GC) and uncovering underling molecular mechanisms. Through immunohistochemistry analysis of 20 pairs of GC and the peritumoral tissues, the expression level of TRIM28 was determined. A variety of assays were applied to explore the important roles of TRIM28 in GC. Western blotting and qRT-PCR analyses were used to analyze the association between TRIM28 and the Wnt/β-catenin signaling pathway. TRIM28 was highly expressed in GC tissues than peritumoral tissues. And high expression level of TRIM28 in GC was associated with good prognostic effects. In vitro functional assays suggested TRIM28 knockdown enhanced the proliferation and clone formation of GC cell. Moreover, TRIM28 knockdown enhanced the expression level of stemness markers, strengthened sphere-forming and drug-resistance properties of GC cells, suggesting important effect on GC cell stemness. Besides, our analysis showed that the Wnt/β-catenin signaling was involved in the effect of TRIM28 on GC cell stemness property, and blocking Wnt/β-catenin signaling pathway obviously rescued the promotion influence of TRIM28 knockdown. Overall, TRIM28 has an important influence on regulating the stem-like property of GC cell via Wnt/β-catenin signaling, suggesting TRIM28 a promising drug target and a potential predictor of prognosis.

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来源期刊
Experimental Biology and Medicine
Experimental Biology and Medicine 医学-医学:研究与实验
CiteScore
6.00
自引率
0.00%
发文量
157
审稿时长
1 months
期刊介绍: Experimental Biology and Medicine (EBM) is a global, peer-reviewed journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences. EBM provides both research and review articles as well as meeting symposia and brief communications. Articles in EBM represent cutting edge research at the overlapping junctions of the biological, physical and engineering sciences that impact upon the health and welfare of the world''s population. Topics covered in EBM include: Anatomy/Pathology; Biochemistry and Molecular Biology; Bioimaging; Biomedical Engineering; Bionanoscience; Cell and Developmental Biology; Endocrinology and Nutrition; Environmental Health/Biomarkers/Precision Medicine; Genomics, Proteomics, and Bioinformatics; Immunology/Microbiology/Virology; Mechanisms of Aging; Neuroscience; Pharmacology and Toxicology; Physiology; Stem Cell Biology; Structural Biology; Systems Biology and Microphysiological Systems; and Translational Research.
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