Research Paper Volume 15, Issue 17 pp 8613—8629
NRP1 regulates autophagy and proliferation of gastric cancer through Wnt/β-catenin signaling pathway
- 1 Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan 430081, Hubei, P.R. China
- 2 Jinan People’s Hospital Affiliated to Shandong First Medical University, Shandong, Jinan City People’s Hospital, Jinan 271199, Shandong, P.R. China
- 3 Beidahuang Group General Hospital, Heilongjiang Province Second Cancer Hospital, Harbin 150000, Heilongjiang, P.R. China
Received: November 19, 2022 Accepted: February 20, 2023 Published: March 7, 2023
https://doi.org/10.18632/aging.204560How to Cite
Copyright: © 2023 Yu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
Abbreviations
OS: Overall survival; DEG: Differentially expressed gene; GEO: Gene Expression Omnibus; CDF: Cumulative distribution function; PCA: Principal components analysis; tSNE: t-distributed stochastic neighbor embedding; ROC: Receiver operating characteristic curve; AUC: Area Under Curve.