Advances in the treatment of nasopharyngeal carcinoma (NPC) have significantly improved the local control rate; however, distant metastasis remains a principal cause of mortality. Previous studies have demonstrated that the expression levels of amyloid β precursor protein (APP) are increased in NPC. The present study aimed to investigate the association between APP and the development of NPC. In order to knockdown APP expression, an APP-small interfering RNA vector was synthesized and transfected into SUNE-1 cells. Cell Counting Kit-8 assay was performed to assess cell viability. The migratory and invasive abilities of SUNE-1 cells were examined by wound healing and Transwell assays, respectively. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to measure the mRNA and protein expression levels of APP, and additional factors involved in epithelial-mesenchymal transition (EMT) and in the mitogen-activated protein kinase (MAPK) signaling pathway. APP silencing significantly suppressed cell viability, migration and invasion. In addition, APP interference downregulated the expression levels of metastasis-associated 1, matrix metalloproteinase (MMP)-2 and MMP-9; however, knockdown of APP led to upregulation of tissue inhibitor of metalloproteinases 2 and inhibited EMT. The phosphorylation levels of p38, extracellular signal-regulated kinases 1/2 and c-Jun N-terminal kinases 1/2 were decreased following downregulation of APP. The present results suggested that APP knockdown may significantly inhibit the development of NPC by suppressing cell viability, migration and invasion, and by inhibiting the EMT process via downregulation of the MAPK signaling pathway. Therefore, APP may facilitate the development of a novel gene therapy for the treatment of NPC.
Chronic rhinosinusitis with nasal polyps (CRSwNP) refers to chronic inflammation of the sinonasal mucosa. It can either be eosinophilic (ECRSwNP) or non-eosinophilic (non-ECRSwNP). However, immune cell infiltration in the microenvironment and pathogenesis of ECRSwNP and non-ECRSwNP are still unclear. The aim of the present study was to assess the immune cell infiltration and molecular mechanisms of ECRSwNP and non-ECRSwNP. In the present study, 22 immune cell types in ECRSwNP and non-ECRSwNP were investigated by CIBERSORT based on transcriptome data. The core gene related pathophysiology of CRSwNP was analyzed using Weighted Gene Correlation Network Analysis according to the phenotype of the infiltrated eosinophils and nasal polyps (NP). A total of four types of immune cells (mast cells, activated dendritic cells, M2 macrophages and activated natural killer cells) were demonstrated to have a direct and indirect correlation with eosinophilic infiltration in ECRSwNP. M1 macrophages and activated CD4 + memory T cells were correlated with major immune cell types in non-ECRSwNP. NP could affect the expression of 'olfactory receptor activity' and 'channel activity' genes to impair the olfactory signaling pathway and neuroactive ligand receptor pathway. 'Cell adhesion molecule binding', 'cytokine receptor binding' and 'glucocorticoid receptor binding' were significantly enriched in ECRSwNP, whereas epithelial cell injury, autophagy and the mTOR pathway (hsa04140 and hsa04150) may serve an important role in the pathogenesis of non-ECRSwNP. There were significantly different immune cell infiltration and related core genes expression characteristics between ECRSwNP and non-ECRSwNP. The results of the present study provide an improved basis for elucidation of the mechanism and treatment of CRSwNP.
Objective This study aimed to explore the mRNA and protein expression of SLC3A2 in laryngeal carcinoma cells and tissues, and functional regulatory mechanism of SLC3A2 in cell ferroptosis of laryngeal carcinoma. Methods We chose the key gene-SLC3A2 of DEGs from TCGA by bioinformatics analysis, and then we constructed stable knockdown of SLC3A2 in laryngeal carcinoma cells. MTT assay and clonogenic assay were used to determine cell viability and cell growth, respectively. The mRNA and protein expression were determined by RT-qPCR and western blotting, respectively. Xenograft tumor model was used to determine the role of SLC3A2 in tumor growth. Results The results of limma analysis recovered that 92 genes were involved in both upregulated DEGs and high risk of poor prognosis, whereas 36 genes were involved in both downregulated DEGs and low risk of poor prognosis. Pathway enrichment analysis indicated that mTOR signaling pathway and ferroptosis exerted a role in regulating these intersection genes. Moreover, SLC3A2 is a key gene in ferroptosis in laryngeal carcinoma. SLC3A2 is highly expressed in laryngeal carcinoma tissues and cells. Patients with high SLC3A2 expression exerted poor survival. SLC3A2 deficiency inhibited cell proliferation and foci formation. Furthermore, knockdown of SLC3A2 expression induced the efficacy of ferroptosis and suppressed ferroptosis related proteins expression. Mechanically, SLC3A2 deficiency facilitated ferroptosis through upregulating the expression of mTOR and P70S6K, whereas inhibited p-mTOR and p-P70S6K expression in laryngeal carcinoma cells. SLC3A2 deficiency inhibited tumorigenesis in nude mice. Conclusion Our study suggests that SLC3A2 negatively regulates ferroptosis through mTOR pathway in laryngeal carcinoma.
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