Trafficking protein TMED3 promotes esophageal squamous cell carcinoma.
Trafficking protein TMED3 promotes esophageal squamous cell carcinoma.
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贩运蛋白TMED3促进食管鳞状细胞癌
DOI：
10.1016/j.bj.2022.03.013
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发表时间：
2023-04
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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作者：
食管鳞状细胞癌（ESCC）的分子机制尚不清楚。跨膜emp24转运蛋白3 （TMED3）在不同的癌症中作为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。采用免疫组织化学、qPCR、western blotting等方法分析TMED3在ESCC组织和细胞中的表达。统计学分析ESCC患者TMED3表达与肿瘤特征的关系。通过功能验证实验和异种移植小鼠模型，研究了TMED3在体外和体内的作用。Affymetrix微阵列和匠心途径分析（Ingenuity Pathway Analysis， IPA）识别出与TMED3功能相关的蛋白。通过功能验证实验分析FAM60A（一种与TMED3功能相关的蛋白）在体外的作用。我们证实TMED3过表达与ESCC患者预后不良相关。当TMED3基因被敲除时，体外可抑制ESCC细胞的增殖、迁移和侵袭，促进细胞凋亡，抑制体内致瘤性。我们进一步揭示了TMED3敲低细胞中基因表达谱的显著变化。在这些差异表达基因中，FAM60A在ESCC组织中过表达。此外，敲除FAM60A显著削弱了ESCC细胞的增殖能力，逆转了TMED3对ESCC细胞的致瘤性。我们的研究揭示了TMED3在ESCC中的致癌作用。
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. 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. 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. Our study revealed an oncogenic role of TMED3 in ESCC.
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影响因子：
--
作者：
Park, Seong-Min;Choi, Eun-Young;Kim, Youn-Jae
通讯作者：
Kim, Youn-Jae
影响因子：
3.7
作者：
Ha, Mihyang;Moon, Hwan;Lee, Dongjun
通讯作者：
Lee, Dongjun
影响因子：
8.8
作者：
Saunders A;Huang X;Fidalgo M;Reimer MH Jr;Faiola F;Ding J;Sánchez-Priego C;Guallar D;Sáenz C;Li D;Wang J
通讯作者：
Wang J
影响因子：
11.1
作者：
Duquet A;Melotti A;Mishra S;Malerba M;Seth C;Conod A;Ruiz i Altaba A
通讯作者：
Ruiz i Altaba A
影响因子：
2.7
作者：
Jerome-Majewska, Loydie A.;Achkar, Tala;Luo, Li;Lupu, Floria;Lacy, Elizabeth
通讯作者：
Lacy, Elizabeth