Rps3 Attenuates Gastric Precancerous Lesions by Promoting Dendritic Cells Maturation via AKT/β-Catenin Pathway

This study aimed to investigate the dysregulated proteins
and the
underlying mechanisms of gastric precancerous lesions. Proteomic and
phosphoproteomic methods were used to characterize the proteome and
phosphoproteome profiles of N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-induced gastric
precancerous lesions. The hub differentially expressed proteins (DEPs)
and phosphoproteins (DEPPs) were identified by using differential
expression and protein–protein interaction network analyses.
Western blot assay, quantitative reverse transcription (qRT)-PCR,
and CCK-8 assays detected the expression of Rps3, N-cadherin, E-cadherin, AKT, p-AKT,
and β-catenin and verified the roles of Rps3 on the MNNG-induced
human gastric epithelial cell line (GES-1) cells. Hub DEPs and phosphoproteins
Rps3, Akt1, and Ctnnb1 were significantly correlated with five dendritic
cells (DCs) pathways, and Akt1 and Ctnnb1 were significantly negatively
correlated with Rps3. MNNG administration markedly reduced the Rps3
mRNA and protein expression levels (all P < 0.05).
Overexpression of Rps3 significantly inhibited tumorigenesis of MNNG-induced
GES-1 cells (all P < 0.01) and changed the protein
levels of N-cadherin, E-cadherin,
AKT, p-AKT, and β-catenin. Similarly, SC79
treatment substantially increased the expression of interleukin (IL)-6, IL-10, and vascular endothelial
growth factor (all P < 0.05). Rps3 was poorly
expressed in precancerous gastric lesions. Correspondingly, overexpression
of Rps3 promoted DC maturation via the AKT/β-catenin pathway,
inhibiting the progression of gastric precancerous lesions.