TEX9 和 eIF3b 在功能上协同作用，促进食管鳞状细胞癌的进展。
TEX9 and eIF3b functionally synergize to promote the progression of esophageal squamous cell carcinoma.
机构信息
Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, 200032, China.
出版信息
BMC Cancer. 2019 Sep 3;19(1):875. doi: 10.1186/s12885-019-6071-9.
BACKGROUND
Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignant digestive tumors around the world. We previously demonstrated that eIF3b could promote the progression of ESCC. The exact mechanisms underlying these effects remained unknown.
METHODS
Quantitative proteomics was applied to detect the potential targets of Eukaryotic translation initiation factor 3 subunit b (eIF3b). RT-qPCR and Western blot were performed to detect the expression of targeted gene and pathway related genes. RNA-immunoprecipitation was applied to verify the binding of eIF3b with targeted gene. Moreover, CCK-8 assay, colony-formation assay, transwell assay, flow cytometry for cell apoptosis and tumor xenograft assay were performed to analyze the regulation of the targeted gene on the bio-function of ESCC cells.
RESULTS
Quantitative proteomics data showed that Testis-expressed protein 9 (TEX9) expression was positively associated with eIF3b expression. RT-qPCR and Western blot results confirmed the quantitative proteomics data and demonstrated that TEX9 expression was positively correlated with TNM stage in ESCC. Furtherly, RNA-immunoprecipitation confirmed that eIF3b binding to TEX9 mRNA. The bio-function related assay demonstrated that TEX9 and eIF3b functionally synergized to promote the proliferation and migration, and inhibited the apoptosis of ESCC cells. In the analysis of mechanism, we revealed that TEX9 and eIF3b promoted the progression of ESCC through the activation of AKT signaling pathway.
CONCLUSIONS
The synergized promoting role of TEX9 and eIF3b in the progression of ESCC may provide a novel mechanism for exploring viable therapeutic strategies for ESCC.
背景
食管鳞状细胞癌（ESCC）是全球最常见的恶性消化道肿瘤之一。我们之前的研究表明，真核翻译起始因子 3 亚基 b（eIF3b）可以促进 ESCC 的进展。但这些作用的确切机制尚不清楚。
方法
应用定量蛋白质组学检测真核翻译起始因子 3 亚基 b（eIF3b）的潜在靶点。采用 RT-qPCR 和 Western blot 检测靶向基因和通路相关基因的表达。应用 RNA-免疫沉淀验证 eIF3b 与靶向基因的结合。此外，通过 CCK-8 测定、集落形成测定、Transwell 测定、细胞凋亡的流式细胞术和肿瘤异种移植测定分析靶向基因对 ESCC 细胞生物功能的调节。
结果
定量蛋白质组学数据显示，睾丸表达蛋白 9（TEX9）的表达与 eIF3b 的表达呈正相关。RT-qPCR 和 Western blot 结果证实了定量蛋白质组学数据，并表明 TEX9 在 ESCC 中的表达与 TNM 分期呈正相关。进一步的 RNA-免疫沉淀证实了 eIF3b 与 TEX9 mRNA 的结合。生物功能相关的测定表明，TEX9 和 eIF3b 协同促进 ESCC 的增殖和迁移，并抑制 ESCC 细胞的凋亡。在机制分析中，我们揭示了 TEX9 和 eIF3b 通过激活 AKT 信号通路促进 ESCC 的进展。
结论
TEX9 和 eIF3b 在 ESCC 进展中的协同促进作用可能为探索 ESCC 可行的治疗策略提供新的机制。
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