Sox11 通过调控 SDCCAG8 促进头颈部癌症的进展。
Sox11 promotes head and neck cancer progression via the regulation of SDCCAG8.
机构信息
School of Dentistry, University of California, Los Angeles, CA, 90095, USA.
Department of Otorhinolaryngology, Key Laboratory of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
出版信息
J Exp Clin Cancer Res. 2019 Mar 29;38(1):138. doi: 10.1186/s13046-019-1146-7.
BACKGROUND
SOX11 is a transcription factor that plays an important role in mantle cell lymphoma development. However, its functional role in head and neck squamous cell carcinoma (HNSCC) remains unknown.
METHODS
Protein expression was measured with Western blotting, immunohistochemistry or quantitative proteomics, and gene expression was measured with quantitative RT-PCR. Functional role of SOX11 in HNSCC was evaluated with MTS/apoptosis, migration, invasion assays and a xenograft model. A SOX11-targeting gene, SDCCAG8, was confirmed with chromatin immunoprecipitation (ChIP), luciferase reporter and rescue assays.
RESULTS
SOX11 was up-regulated in recurrent versus primary HNSCC and in highly invasive versus low invasive HNSCC cell lines. Silencing SOX11 in HNSCC cell lines significantly inhibited the cell proliferation, migration, invasion and resistance to Cisplatin, and vice versa. Quantitative proteomic analysis of SOX11-silencing HNSCC cells revealed a number of differentially expressed proteins, including a down-regulated tumor antigen SDCCAG8. Silencing of SDCCAG8 in HNSCC cells also significantly inhibited the cell proliferation, migration and invasion, and vice versa. ChIP assays demonstrated that endogenous SOX11 strongly bound to Sdccag8 gene promoter in highly invasive HNSCC cells. When over-expressed in low invasive HNSCC cells, wild type SOX11 but not mutant SOX11 induced the promoter activity of Sdccag8 and significantly induced the expression of SDCCAG8. However, exogenous mutant SOX11 abolished the expression of SDCCAG8 in highly invasive HNSCC cells. In addition, the inhibitory effects of SOX11 knockdown were partially rescued by over-expression of SDCCAG8 in HNSCC cells.
CONCLUSION
Collectively, our findings indicate SOX11 promotes HNSCC progression via the regulation of SDCCAG8.
背景
SOX11 是一种转录因子，在套细胞淋巴瘤的发展中发挥重要作用。然而，其在头颈部鳞状细胞癌（HNSCC）中的功能作用尚不清楚。
方法
使用 Western blot、免疫组织化学或定量蛋白质组学测量蛋白质表达，使用定量 RT-PCR 测量基因表达。使用 MTS/凋亡、迁移、侵袭测定和异种移植模型评估 SOX11 在 HNSCC 中的功能作用。使用染色质免疫沉淀（ChIP）、荧光素酶报告基因和拯救测定验证 SOX11 靶向基因 SDCCAG8。
结果
SOX11 在复发性与原发性 HNSCC 以及高侵袭性与低侵袭性 HNSCC 细胞系中上调。在 HNSCC 细胞系中沉默 SOX11 显著抑制细胞增殖、迁移、侵袭和对顺铂的耐药性，反之亦然。SOX11 沉默 HNSCC 细胞的定量蛋白质组学分析揭示了许多差异表达的蛋白质，包括下调的肿瘤抗原 SDCCAG8。SDCCAG8 在 HNSCC 细胞中的沉默也显著抑制了细胞增殖、迁移和侵袭，反之亦然。ChIP 测定表明，内源性 SOX11 在高侵袭性 HNSCC 细胞中强烈结合于 Sdccag8 基因启动子。当在低侵袭性 HNSCC 细胞中过表达时，野生型 SOX11 而非突变型 SOX11 诱导 Sdccag8 启动子活性，并显著诱导 SDCCAG8 的表达。然而，外源性突变型 SOX11 则可消除高侵袭性 HNSCC 细胞中 SDCCAG8 的表达。此外，在 HNSCC 细胞中过表达 SDCCAG8 部分挽救了 SOX11 敲低的抑制作用。
结论
综上所述，我们的研究结果表明 SOX11 通过调节 SDCCAG8 促进 HNSCC 进展。
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