Abstract
BackgroundEsophageal 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.MethodsQuantitative 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.ResultsQuantitative 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.ConclusionsThe synergized promoting role of TEX9 and eIF3b in the progression of ESCC may provide a novel mechanism for exploring viable therapeutic strategies for ESCC.
Highlights
Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignant digestive tumors around the world
Testis-expressed protein 9 (TEX9) expression is associated with Eukaryotic translation initiation factor 3 subunit b (eIF3b) expression and TNM stage in ESCC Quantitative proteomics was performed in eIF3b-depleted, eIF3b-overexpressed and normal control of EC109 cells
We proved that TEX9 expression was increased significantly in eIF3b-overexpressed EC109 and decreased significantly in eIF3b-depleted EC109 (Fig. 1c), which indicated that Western blot results confirmed quantitative proteomics
Summary
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. Esophageal carcinoma is one of the most frequent digestive malignant tumors around the world and ESCC is the major pathological type in China [1]. Deregulated protein synthesis and degradation contribute to cancer genesis and progression. EIF3b is aberrantly expressed or activated in different types of human cancer. It promoted proliferation and inhibited apoptosis in glioblastoma cells [5]. To identify the mechanisms underlying these effects, especially whether through alterations in the rates of synthesis of specific proteins, quantitative proteomics was considered in this study
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