Background: Recurrence and distant metastasis are still the main factors leading to treatment failure for malignant tumors including nasopharyngeal carcinoma (NPC). Therefore, elucidating the molecular mechanisms underlying nasopharyngeal carcinoma metastasis is of great clinical significance for targeted gene therapy and prognostic evaluation. PinX1, a tumor suppressor gene, was previously demonstrated to be a powerful tool for targeting telomerase in order to resist malignant tumor proliferation and migration. The aim of this study was to explore the mechanism through which PinX1 regulates epithelial-mesenchymal transition (EMT) and tumor metastasis in NPC and investigate its clinical significance and biological role with respect to disease progression.Methods: Cell Counting Kit-8 (CCK8), Transwell assays, Colony formation analysis and Xenograft tumorigenicity assay were used to measure the nasopharyngeal CD133 + cancer stem cell proliferation, migration, and invasion abilities. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assays were conducted to investigate the underlying mechanism that PinX1 inhibits cell proliferation, migration, and invasion via regulating EMT in nasopharyngeal CD133 + CSCs. Results: We found that the overexpression of PinX1 and P53 inhibited cell proliferation, migration, and invasion, but that the inhibition of miR-200b blocked these effects, in nasopharyngeal CD133 + cancer stem cells (CSCs). Mechanistic investigations elucidated that PinX1 inhibits cell proliferation, migration, and invasion by regulating the P53/miR-200b-mediated transcriptional suppression of Snail1, Twist1, and Zeb1, consequently inhibiting EMT in nasopharyngeal CD133 + CSCs. Conclusions: Our findings indicate that PinX1 inhibits cell proliferation, migration, and invasion via P53/miR-200bregulated EMT in the malignant progression of human NPC, which might suggest novel clinical implications for disease treatment.
Background: According to statistics, even with active treatment, the recurrence rate of HNSCC is at 40%-50%. Head and neck cancer remains a challenge for otolaryngologists. Therefore, the identification of new biomarkers is an urgent need for the diagnosis, treatment, and prognosis of malignant tumors of the head and neck. Methods: In this study, transcriptome data from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database were used to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was performed to identify gene modules and hub genes related to head and neck squamous cell carcinoma (HNSCC). Protei-Protei interaction(PPI) network and Cytoscape software were used to analyze the protein interaction network. HNSCC clinical data from the TCGA and Gene Expression Profile Interactive Analysis 2 databases were used to analyze the survival rate of hub genes, and the correlation between hub genes and tumor stage was further analyzed.Results: A total of 2836 and 570 DEGs were identified from the TCGA expression data and GEO gene chip datasets, respectively. We found that the green module had the highest correlation with HNSCC. A total of 15 hub genes were also identified. In the Human Protein Atlas database, we found that thioredoxin reductase 1 (TXNRD1) was overexpressed in HNSCC tumors compared with normal tissues at the transcriptional level. Survival analysis also suggested that TXNRD1 was a poor prognostic factor for HNSCC.Conclusion: Our results indicate that TXNRD1 is very likely to be identified as a potential biomarker and target for HNSCC. However, further research is required to fully reveal its role in HNSCC pathogenesis as well as its value as a prognostic biomarker.
BackgroundThe role of PinX1 in tumorigenesis and development has been extensively studied. We have previously reported roles for PinX1 in modulating proliferation, apoptosis, EMT, and stemness in NPC cells. However, the relationship between PinX1, autophagy, and cell function in NPC remains unclear. The aim of this study was to explore the mechanisms by which PinX1 regulates autophagy in NPC, and to investigate its clinical significance and biological role with respect to disease progression. MethodsMTT and xenograft tumorigenicity assays were used to assess the proliferative capacity of NPC cells. Autophagic flux was monitored using a tandem monomeric DAPI–FITC–LC3 reporter assay. The rates of apoptosis and the cell cycle in NPC cells were analyzed using flow cytometry. Reverse-transcription quantitative PCR was used to evaluate the expression of hTERT and PinX1. Western blot analysis was used to evaluate the activation of autophagy and the signaling status of the AKT/mTOR and NF-κB/p65 pathways. ResultsPinX1 overexpression induced autophagy and apoptosis, while suppressing NPC cell proliferation, migration, and invasion, and decelerated cell-cycle progression; inhibiting autophagy via 3-methyladenine reversed these outcomes. Mechanistic investigations clarified that PinX1 overexpression significantly reduced the expression of p-AKT, p-mTOR, p65, and p-p65. Chloroquine treatment in PinX1-overexpressing cells did not significantly alter p-AKT and p-mTOR levels, whereas 3-MA treatment in PinX1-overexpressing cells resulted in increased p65 and p-p65 expression, relative to untreated PinX1-overexpressing cells.ConclusionThese findings indicate that PinX1 promotes autophagy by inhibiting the AKT/mTOR signaling pathway; this, in turn, inhibits the NF-κB/p65 signaling pathway, thereby inhibiting cell proliferation and induces cell apoptosis in NPC cells.
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