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TSR2 Induces laryngeal cancer cell apoptosis through inhibiting NF-κB signaling pathway
Hong-Jiang He1, Han Bing2, Guijun Liu3
1Department of Head and Neck Surgery, Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
Objectives/Hypothesis:
Human 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 Design:
The 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.
Methods:
We 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-κB) p65 nuclear translocation through Western blot and terminal dUTP nick end-labeling assays.
Results:
We 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-κB signaling pathway via decreasing nuclear NF-κB p65 and increasing cytoplasm NF-κB p65. Moreover, overexpression of TSR2 significantly inhibited the phosphorylation of IκBα and IKKα/β.
Conclusions:
The results indicated that TSR2-induced apoptosis was mediated by inhibiting the NF-κB signaling pathway, which may provide an effective target in gene therapy for LSCC.
Level Of Evidence:
NA. Laryngoscope, 128:E130-E134, 2018.
Insights
TSR2 is downregulated in laryngeal squamous cell carcinoma (LSCC). Overexpressing TSR2 promotes LSCC cell apoptosis by inhibiting the NF-κB signaling pathway, offering a potential gene therapy target.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Human laryngeal squamous cell carcinoma (LSCC) is a malignancy originating in the laryngeal mucosa epithelium.
- The precise molecular mechanisms driving LSCC progression remain unclear.
- Investigating novel molecular targets is crucial for developing effective LSCC therapies.
Purpose of the Study:
- To elucidate the role of TSR2 in LSCC.
- To investigate the molecular mechanisms by which TSR2 influences LSCC cell apoptosis.
- To explore TSR2 as a potential therapeutic target for LSCC.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) to assess TSR2 expression in LSCC tissues and cells.
- Overexpression of TSR2 in LSCC cell lines (Hep-2 and AMC-HN-8) using pcDNA3.1-TSR2.
- Western blot and terminal dUTP nick end-labeling assays to evaluate apoptosis-related proteins and NF-κB p65 nuclear translocation.
Main Results:
- TSR2 was found to be significantly downregulated in LSCC tissues and cells compared to normal controls.
- Overexpression of TSR2 promoted apoptosis in LSCC cells and upregulated apoptosis-related proteins.
- TSR2 overexpression inhibited the NF-κB signaling pathway by reducing nuclear NF-κB p65 and increasing cytoplasmic NF-κB p65, while also inhibiting IκBα and IKKα/β phosphorylation.
Conclusions:
- TSR2 plays a suppressive role in LSCC development.
- TSR2-induced apoptosis in LSCC is mediated through the inhibition of the NF-κB signaling pathway.
- TSR2 represents a promising molecular target for gene therapy in LSCC treatment.
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