研究动态
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NRP1通过Wnt/β-连环蛋白信号通路调控胃癌的自噬和增殖。

NRP1 regulates autophagy and proliferation of gastric cancer through Wnt/β-catenin signaling pathway.

发表日期:2023 Mar 07
作者: Qi-Ying Yu, Yue Han, Jia-Hui Lu, Yan-Jie Sun, Xing-Hua Liao
来源: GENES & DEVELOPMENT

摘要:

胃癌的致死率较高,其复杂的分子病理机制导致治疗结果不理想。自噬在癌症中发挥促进和抑制的双重作用。然而,在胃癌中自噬的作用仍然不明确。因此,在本研究中,我们首先从人类自噬数据库中获得自噬相关基因,然后应用一致性聚类分析来分析TCGA数据库中胃癌样本的分子亚型。在亚型分型后获得的基因然后用来构建风险预测模型。随后,通过PCA和tSNE评估胃癌样本的风险得分,结果表明具有很好的判别能力。Cox回归分析结果和时间依赖ROC曲线分析表明该模型具有良好的风险预测能力。最后,在表达配对分析、Kaplan-Meier曲线和GEO数据集的外部验证中选择NRP1作为最终研究对象。体外实验显示NRP1通过影响Wnt/β-catenin信号通路调节胃癌细胞的增殖和自噬能力。类似地,体内实验显示NRP1可以影响体内肿瘤的生长。因此,我们提出NRP1可以通过调节胃癌中自噬的方式作为预后因子和治疗靶点。
Gastric cancer possesses high lethality rate, and its complex molecular mechanisms of pathogenesis lead to irrational treatment outcomes. Autophagy plays a dual role in cancer by both promoting and suppressing the cancer. However, the role of autophagy in gastric cancer is still vague. Therefore, in this study, we first obtained autophagy-related genes from the Human Autophagy Database, and then applied consensus clustering analysis to analyse the molecular subtypes of gastric cancer samples in the TCGA database. The genes obtained after subtyping were then applied to construct risk prognostic model. Following this, PCA and tSNE assessed risk scores with good discriminatory ability for gastric cancer samples. The results of Cox regression analysis and time-dependent ROC curve analysis indicated that the model had good risk prediction ability. Finally, NRP1 was selected as the final study subject in the context of expression pairwise analysis, Kaplan-Meier curves and external validation of the GEO dataset. In vitro experiments showed that NRP1 has the ability to regulate the proliferation and autophagy of gastric cancer cells by affecting the Wnt/β-catenin signalling pathway. Similarly, in vivo experiments have shown that NRP1 can affect tumour growth in vivo. We therefore propose that NRP1 can be used as both a prognostic factor and a therapeutic target through the regulation of autophagy in gastric cancer.