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Abstract：
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.
摘要：
TRIM28对胃癌发生的影响以及潜在的分子机制仍有待研究。我们旨在探索TRIM28对胃癌（GC）的重要作用，并揭示其潜在的分子机制。通过对20对GC及瘤周组织的免疫组化分析,确定TRIM28的表达水平。采用多种方法探讨了TRIM28在GC中的重要作用。使用蛋白质印迹和qRT-PCR分析来分析TRIM28与Wnt/β-catenin信号通路之间的关联。TRIM28在GC组织中比瘤周组织高表达。TRIM28在GC中的高表达水平与良好的预后效果相关。体外功能测定表明TRIM28敲低增强了GC细胞的增殖和克隆形成。此外，TRIM28敲低增强了干性标志物的表达水平，增强GC细胞的球体形成和耐药特性，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信号参与了TRIM28对GC细胞干性的影响，阻断Wnt/β-catenin信号通路可明显挽救TRIM28敲低的促进作用。总的来说,TRIM28通过Wnt/β-catenin信号通路对GC细胞的干细胞样特性具有重要的调控作用,提示TRIM28是一个有希望的药物靶标和潜在的预后预测指标。
