Protein phosphatase 1 regulatory subunit 15 A (PPP1R15A) promoted the progression of gastric cancer by activating cell autophagy under energy stress

作者：Yingnan Cui, Xueyuan Cao, Yangyu Zhang, Chunli Fu, Dongming Li, Yuanlin Sun, Yuzheng Zhang, Tingshuang Xu, Tetsuya Tsukamoto, Donghui Cao, Jing Jiang · 发表于：Journal of Experimental & Clinical Cancer Research · 年份：2025 · DOI：10.1186/s13046-025-03320-y · 被引用次数：11 · 研究领域：Protein Tyrosine Phosphatases、Cancer, Hypoxia, and Metabolism、Autophagy in Disease and Therapy

BACKGROUND: Glucose metabolism plays a critical role in tumor progression. When glucose intake is insufficient and the tumor's growth rate exceeds its energy supply, tumor cells typically adapt and overcome the energy stress through compensatory mechanisms to maintain the survival of tumor cells, which may also be related to tumor recurrence or metastasis. METHODS: Different concentrations of glucose were selected as the basis for the energy stress model of gastric cancer. Then CCK-8 and flow cytometry were used to detect its effects on cell proliferation, apoptosis, and cell cycle. Differentially expressed genes (DEGs) were screened by RNA sequencing and the regulated pathways were identified by gene set enrichment analysis. The regulatory relationship between the gene PPP1R15A and its transcription factor JUN was proved by ChIP-qPCR and dual-luciferase reporter assay. The gain and loss of function assays were conducted to examine the effects of PPP1R15A under energy stress in vivo and in vitro. Potential regulatory mechanisms of PPP1R15A were further analyzed through a combination of online databases, RNA sequencing, and metabolite sequencing. The regulation of PPP1R15A on cell autophagy under energy stress was detected by western blot, transmission electron microscope, mRFP-GFP-LC3 adenovirus and laser scanning confocal microscopy. RESULTS: PPP1R15A and the transcription factor JUN were significantly upregulated by glucose deprivation (0 mM vs. 25 mM), JUN combined with th...