He Hong-Jiang, Bing Han, Liu Guijun
Department of Head and Neck Surgery, Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
Department of Ophthalmology, Hospital of Heilongjiang Province, Harbin, China.
Laryngoscope. 2018 Apr;128(4):E130-E134. doi: 10.1002/lary.27035. Epub 2017 Dec 27.
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.
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.
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.
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.
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.
NA. Laryngoscope, 128:E130-E134, 2018.
目的/假设：人喉鳞状细胞癌（LSCC）是一种最初在喉黏膜上皮组织中发现的恶性肿瘤。然而，其潜在的分子机制仍不清楚。在本研究中，我们旨在探讨TSR2在LSCC细胞凋亡中的潜在分子机制。
首先分析TSR2在LSCC组织中的表达。然后通过过表达pcDNA3.1-TSR2对TSR2在Hep-2和AMC-HN-8细胞系中的功能作用进行研究。
我们通过定量实时聚合酶链反应（qRT-PCR）研究TSR2在LSCC组织和细胞中的表达水平。构建pcDNA3.1-TSR2以探讨在Hep-2细胞和AMC-HN-8细胞中过表达TSR2的作用。我们通过蛋白质免疫印迹法和末端脱氧核苷酸转移酶介导的缺口末端标记法进一步研究过表达TSR2对细胞凋亡相关蛋白和活化B细胞核因子κB（NF-κB）p65核转位的影响。
我们发现与对照组相比，TSR2在LSSC组织和细胞中表达下调，并且在Hep-2和AMC-HN-8细胞中过表达TSR2可促进细胞凋亡及相关凋亡蛋白表达。蛋白质免疫印迹法/qRT-PCR数据进一步表明，在Hep-2和AMC-HN-8细胞中过表达TSR2可通过减少细胞核内NF-κB p65并增加细胞质中NF-κB p65来导致NF-κB信号通路受阻。此外，过表达TSR2可显著抑制IκBα和IKKα/β的磷酸化。
结果表明TSR2诱导的细胞凋亡是通过抑制NF-κB信号通路介导的，这可能为LSCC的基因治疗提供一个有效的靶点。
无。《喉镜》，2018年，第128卷：E130-E134页
