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

Abstract

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.

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“…Again, they are both involved in promoting angiogenesis, NRP1 as a co-receptor of VEGFR2 and both by stabilizing HIF-1alfa to activate VEGF expression [50][51][52]. Finally, the Wnt pathway, a key player in oncogenesis, is triggered not only by Wnt5a, but also by other targets of the network, i.e., NRP1, and YY1 [27,[53][54][55][56].…”