trafficking protein TMED3 promotes esophageal squamous cell carcinoma.
Trafficking protein TMED3 promotes esophageal squamous cell carcinoma.
机构信息
Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
出版信息
Biomed J. 2023 Apr;46(2):100528. doi: 10.1016/j.bj.2022.03.013. Epub 2022 Mar 28.
BACKGROUND
The molecular mechanisms of esophageal squamous cell carcinoma (ESCC) remain poorly understood. Transmembrane emp24 trafficking protein 3 (TMED3) acts as an oncogene or tumor suppressor gene in different cancers. Our study was to explore the clinicopathological significance and functional roles of TMED3 in ESCC.
METHODS
Immunohistochemistry, qPCR, and western blotting were used to analyze the expression of TMED3 in ESCC tissues and cells. Statistical analysis was performed to analyze the relationship between TMED3 expression and tumor characteristics in patients with ESCC. The role of TMED3 in vitro and in vivo was investigated by performing functional verification experiments and using a xenograft mouse model. Proteins that are functionally related to TMED3 were recognized by Affymetrix microarray and Ingenuity Pathway Analysis (IPA). Functional verification experiments were performed to analyze the role of FAM60A (a protein functionally related to TMED3) in vitro.
RESULTS
We confirmed the overexpression of TMED3 was correlated with poor prognosis in ESCC patients. When TMED3 was knocked down, ESCC cell proliferation, migration, and invasion were inhibited whereas cell apoptosis was promoted in vitro, and tumorigenicity was inhibited in vivo. We further revealed significant changes in gene expression profile in TMED3 knockdown cells. Among these differentially expressed genes, FAM60A was overexpressed in ESCC tissues. Furthermore, knocking down FAM60A significantly weakened the proliferation ability of ESCC cells and reversed TMED3's tumorigenicity of ESCC cells.
CONCLUSION
Our study revealed an oncogenic role of TMED3 in ESCC.
背景
食管鳞状细胞癌（ESCC）的分子机制仍知之甚少。跨膜 emp24 转运蛋白 3（TMED3）在不同的癌症中充当癌基因或肿瘤抑制基因。我们的研究旨在探讨 TMED3 在 ESCC 中的临床病理意义和功能作用。
方法
使用免疫组织化学、qPCR 和 Western blot 分析 TMED3 在 ESCC 组织和细胞中的表达。统计分析用于分析 TMED3 表达与 ESCC 患者肿瘤特征之间的关系。通过进行功能验证实验和使用异种移植小鼠模型研究 TMED3 在体外和体内的作用。通过 Affymetrix 微阵列和 IPA（Ingenuity Pathway Analysis）识别与 TMED3 功能相关的蛋白质。进行功能验证实验以分析 FAM60A（与 TMED3 功能相关的蛋白质）在体外的作用。
结果
我们证实 TMED3 的过表达与 ESCC 患者的不良预后相关。当 TMED3 被敲低时，ESCC 细胞的增殖、迁移和侵袭在体外受到抑制，而细胞凋亡受到促进，体内肿瘤生成受到抑制。我们进一步揭示了 TMED3 敲低细胞中基因表达谱的显著变化。在这些差异表达的基因中，FAM60A 在 ESCC 组织中过表达。此外，敲低 FAM60A 显著削弱了 ESCC 细胞的增殖能力，并逆转了 TMED3 对 ESCC 细胞的致瘤性。
结论
我们的研究揭示了 TMED3 在 ESCC 中的致癌作用。
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