PinX1-Induced Autophagy Inhibits Cell Proliferation and Induces Cell Apoptosis by Inhibiting the NF-κB/p65 Signaling Pathway in Nasopharyngeal Carcinoma

Abstract 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.