Dataset Information

MYH9 promotes cell metastasis via inducing Angiogenesis and Epithelial Mesenchymal Transition in Esophageal Squamous Cell Carcinoma.

ABSTRACT: Non-muscle myosin heavy chain 9 (MYH9) is one novel low frequency mutated gene identified in esophageal squamous cell carcinoma (ESCC) using next-generation sequencing. However, its clinical relevance, potential function and mechanisms remain elusive. Methods: Genomic sequencing datas from 104 esophageal squamous cell carcinoma (ESCC) cases were screened a series of low frequency mutant genes. MYH9 was selected to further analyze its clinical significance, function and PCR-array was performed to explore its potential mechanism. Results: MHY9 is a low frequency mutant gene with a mutation frequency of 2.88% in ESCC. Immunohistochemical analysis showed that MYH9 expression was significantly higher in ESCC tumor tissues, and the expression levels were associated with lymph node metastasis of ESCC patients. Moreover, we found that MYH9 knock-down led to inhibition of cell migration and invasion. PCR-array showed MYH9 knockdown led to a significant change of genes expression associated with angiogenesis and epithelial-to-mesenchymal transition (EMT). This observation is further confirmed in TCGA database of LUSC (lung squamous cell carcinoma), CESC (cervical squamous cell carcinomas) and HNSC (head and neck squamous cell carcinoma). Conclusions: Collectively, our study identifies a novel role and mechanism of MYH9, highlights a significance of MYH9 as a metastatic biomarker, and offers potential therapeutic targets for ESCC patients harboring MYH9 mutations.

SUBMITTER: Yang B

PROVIDER: S-EPMC7415390 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MYH9 promotes cell metastasis via inducing Angiogenesis and Epithelial Mesenchymal Transition in Esophageal Squamous Cell Carcinoma.

Yang Bin B Liu Huijuan H Bi Yanghui Y Cheng Caixia C Li Guodong G Kong Pengzhou P Zhang Ling L Shi Ruyi R Zhang Yunkui Y Zhang Rongsheng R Cheng Xiaolong X

International journal of medical sciences 20200725 13

Non-muscle myosin heavy chain 9 (MYH9) is one novel low frequency mutated gene identified in esophageal squamous cell carcinoma (ESCC) using next-generation sequencing. However, its clinical relevance, potential function and mechanisms remain elusive. Methods: Genomic sequencing datas from 104 esophageal squamous cell carcinoma (ESCC) cases were screened a series of low frequency mutant genes. MYH9 was selected to further analyze its clinical significance, function and PCR-a ...[more]

PMID: 32788880

Similar Datasets

Project description:BackgroundEvading immune surveillance is necessary for tumor metastasis. Thus, there is an urgent need to better understand the interaction between metastasis and mechanisms of tumor immune evasion. In this study, we aimed to clarify a novel mechanism that link tumor metastasis and immunosuppression in the development of esophageal squamous cell carcinoma (ESCC).MethodsThe expression of melanoma-associated antigen C3 (MAGE-C3) was detected using immunohistochemistry. Transwell assays were used to evaluate the migration and invasion ability of esophageal squamous cell carcinoma (ESCC) cells. Metastasis assays in mice were used to evaluate metastatic ability in vivo. Lymphocyte-mediated cytotoxicity assays were performed to visualize the immune suppression function on tumor cells. RNA sequencing was performed to identify differentially expressed genes between MAGE-C3 overexpressing ESCC cells and control cells. Gene ontology (GO) enrichment analyses was performed to identify the most altered pathways influenced by MAGE-C3. The activation of the interferon-γ (IFN-γ) pathway was analyzed using Western blotting, GAS luciferase reporter assays, immunofluorescence, and flow cytometry. The role of MAGE-C3 in the IFN-γ pathway was determined by Western blotting and immunoprecipitation. Furthermore, immunohistochemistry and flow cytometry analysis monitored the changes of infiltrated T cell populations in murine lung metastases.ResultsMAGE-C3 was overexpressed in ESCC tissues. High expression of MAGE-C3 had a significant association with the risk of lymphatic metastasis and poor survival in patients with ESCC. Functional experiments revealed that MAGE-C3 promoted tumor metastasis by activating the epithelial-mesenchymal transition (EMT). MAGE-C3 repressed antitumor immunity and regulated cytokine secretion of T cells, implying an immunosuppressive function. Mechanistically, MAGE-C3 facilitated IFN-γ signaling and upregulated programmed cell death ligand 1 (PD-L1) by binding with IFN-γ receptor 1 (IFNGR1) and strengthening the interaction between IFNGR1 and signal transducer and activator of transcription 1 (STAT1). Interestingly, MAGE-C3 displayed higher tumorigenesis in immune-competent mice than in immune-deficient nude mice, confirming the immunosuppressive role of MAGE-C3. Furthermore, mice bearing MAGE-C3-overexpressing tumors showed worse survival and more lung metastases with decreased CD8+ infiltrated T cells and increased programmed cell death 1 (PD-1)+ CD8+ infiltrated T cells.ConclusionMAGE-C3 enhances tumor metastasis through promoting EMT and protecting tumors from immune surveillance, and could be a potential prognostic marker and therapeutic target.

Dataset Information

MYH9 promotes cell metastasis via inducing Angiogenesis and Epithelial Mesenchymal Transition in Esophageal Squamous Cell Carcinoma.

Publications

MYH9 promotes cell metastasis <i>via</i> inducing Angiogenesis and Epithelial Mesenchymal Transition in Esophageal Squamous Cell Carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets