【摘要】 目的筛选胃癌中具有临床意义的潜在药物靶点并研究此靶点蛋白在胃癌发生、发展中的功能和潜在分子机制。方法通过临床数据库GEPIA分别找到在胃癌中高表达的基因(tumor/normal>2)以及在胃癌中具有显著临床预后相关性的基因(P<0.05),将这两部分基因进行重合分析找到具有显著临床意义的靶基因,进一步通过高表达预后差原则筛选到目的靶基因;通过30组临床样品研究FAM198B在胃癌以及临近正常组织中的表达特征;通过siRNA介导敲低目的基因的表达,利用细胞增殖实验和划痕迁移实验验证目的基因在胃癌发生、发展中的重要性;最后通过分析与目的基因共表达基因参与的信号通路,探索目的基因在胃癌中发挥功能的潜在分子机制,进一步通过蛋白免疫印迹实验进行验证。结果共有46个基因在胃癌中高表达且具有显著临床预后相关性;FAM198B在胃癌中显著高表达,且高表达的患者具有不良预后,FAM198B在30组临床胃癌组织中较正常组织显著高表达;敲低FAM198B抑制胃癌细胞的生长增殖和迁移;敲低FAM198B降低PI3K、AKT的磷酸化,但本底表达保持不变,可能通过PI3K-AKT信号通路参与胃癌的发生、发展。结论 FAM198B高表达诱导PI3K、AKT的磷酸化,可能通过参与PI3K-AKT信号通路促进胃癌细胞生长增殖和迁移。更多还原

【Abstract】 Objective To screen clinically significant potential drug targets in gastric cancer and study the function and potential molecular mechanisms of this target protein in the development of gastric cancer.Methods We found genes that were highly expressed in gastric cancer(tumor/normal>2) and genes that had significant clinical prognostic correlation in gastric cancer(P<0.05) by the clinical database GEPIA. The overlapping analysis of these two genes was performed to find target genes with significantly clinical significance. The target genes were further screened by the principle of high expression and poor prognosis; 30 groups of clinical samples were used to study the expression characteristics of FAM198 B in gastric cancer and adjacent normal tissues; the expression of the target gene was knocked down by siRNA, and cell proliferation experiments and scratch migration experiments were used to verify the importance of the target gene in the occurrence and development of gastric cancer. Finally, by analyzing the signal pathways involved in co-expressing genes with the target gene, the potential molecular mechanism of the target gene’s function in gastric cancer was explored, and further verified by Western blotting experiments. Results A total of 46 genes were highly expressed in gastric cancer and had significantly clinical prognostic relevance; FAM198 B was significantly overexpressed in gastric cancer, and patients with high expression had a poor prognosis. FAM198 B was significantly more highly expressed in 30 gastric cancer tissues than normal tissues; knockdown of FAM198 B inhibited the proliferation and migration of gastric cancer cells; knockdown of FAM198 B decreased the phosphorylation of PI3 K and AKT, however, the background expression remained unchanged, which may be involved in the occurrence and development of gastric cancer through the PI3 K-AKT signaling pathway. Conclusion High expression of FAM198 B induces the phosphorylation of PI3 K and AKT, thereby participating in the PI3 K-AKT signaling pathway to promote the proliferation and migration of gastric cancer cells.更多还原