TSR2 Induces laryngeal cancer cell apoptosis through inhibiting NF-B signaling pathway

Objectives/HypothesisHuman laryngeal squamous cell carcinoma (LSCC) is a malignancy that was discovered originally in the epithelial tissue of laryngeal mucosa. However, the underlying molecular mechanism is still not clear. In this study, we aimed to investigate the potential molecular mechanisms of TSR2 in the LSCC cell apoptosis. Study DesignThe expression of TSR2 was first analyzed in LSCC tissues. Then functional effects of TSR2 on Hep-2 and AMC-HN-8 cell lines were performed by overexpression pcDNA3.1-TSR2. MethodsWe investigated the expression level of TSR2 in LSCC tissues and cells by performing quantitative real-time polymerase chain reaction (qRT-PCR). The pcDNA3.1-TSR2 was constructed to explore the effect of overexpressing TSR2 in Hep-2 cells and AMC-HN-8 cells. We further investigated the effect of overexpressing TSR2 on cell apoptosis-related protein and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B) p65 nuclear translocation through Western blot and terminal dUTP nick end-labeling assays. ResultsWe found that TSR2 was downregulated in LSSC tissues and cells compared with the controls, and the overexpression of TSR2 in Hep-2 and AMC-HN-8 cells could promote cell apoptosis and related apoptosis proteins. The Western blot/qRT-PCR data further indicated that overexpression of TSR2 in Hep-2 and AMC-HN-8 cells could lead to a block of NF-B signaling pathway via decreasing nuclear NF-B p65 and increasing cytoplasm NF-B p65. Moreover, overexpression of TSR2 significantly inhibited the phosphorylation of IB and IKK/. ConclusionsThe results indicated that TSR2-induced apoptosis was mediated by inhibiting the NF-B signaling pathway, which may provide an effective target in gene therapy for LSCC. Level of EvidenceNA. Laryngoscope, 128:E130-E134, 2018