MicroRNA-146a suppresses tumor malignancy via targeting vimentin in esophageal squamous cell carcinoma cells with lower fibronectin membrane assembly
Abstract Background Esophageal squamous cell carcinoma (ESCC) is widely prevalent in Taiwan, and high metastatic spread of ESCC leads to poor survival rate. Fibronectin (FN) assembly on the cell membrane may induce ESCC mobility. MicroRNAs (MiRNAs) are abundant in and participate in tumorigenesis in...
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BMC
2020-11-01
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Series: | Journal of Biomedical Science |
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Online Access: | https://doi.org/10.1186/s12929-020-00693-4 |
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author | Hong-Yi Chang Chi-Hua Lee Yi-Syuan Li Jing-Tong Huang Sheng-Hui Lan Yi-Fang Wang Wu-Wei Lai Yi-Ching Wang Yan-Ju Lin Hsiao-Sheng Liu Hung-Chi Cheng |
author_facet | Hong-Yi Chang Chi-Hua Lee Yi-Syuan Li Jing-Tong Huang Sheng-Hui Lan Yi-Fang Wang Wu-Wei Lai Yi-Ching Wang Yan-Ju Lin Hsiao-Sheng Liu Hung-Chi Cheng |
author_sort | Hong-Yi Chang |
collection | DOAJ |
description | Abstract Background Esophageal squamous cell carcinoma (ESCC) is widely prevalent in Taiwan, and high metastatic spread of ESCC leads to poor survival rate. Fibronectin (FN) assembly on the cell membrane may induce ESCC mobility. MicroRNAs (MiRNAs) are abundant in and participate in tumorigenesis in many cancers. However, the role of MiRNA in FN assembly-related ESCC mobility remains unexplored. Methods We divided ESCC CE81T cells into high-FN assembly (CE81FN+) and low-FN assembly (CE81FN−) groups by flow cytometry. MiRNA microarray analysis identified miR-146a expression as the most down-regulated miRNA in comparison of CE81FN+ and CE81FN− cells. Results Cell proliferation and migration were decreased when CE81FN+ cells overexpressed transgenic miR-146a compared to the parental cells, indicating an inverse correlation between low miR-146a expression and high proliferation as well as motility of FN assembly ESCC cells. Furthermore, vimentin is the target gene of miR-146a involved in ESCC tumorigenesis. MiR-146a suppressed cell proliferation, migration and invasion of CE81FN+ cells through the inhibition of vimentin expression, as confirmed by real-time PCR, Western blotting and Transwell™ assay. Analysis of one hundred and thirty-six paired ESCC patient specimens revealed that low miR-146a and high vimentin levels were frequently detected in tumor, and that the former was associated with late tumor stages (III and IV). Notably, either low miR-146a expression or high vimentin level was significantly associated with poor overall survival rate among ESCC patients. Conclusions This is the first report to link FN assembly in the cell membrane with miR-146a, vimentin and ESCC tumorigenesis both in vitro and in ESCC patients. |
first_indexed | 2024-12-24T05:24:24Z |
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institution | Directory Open Access Journal |
issn | 1423-0127 |
language | English |
last_indexed | 2024-12-24T05:24:24Z |
publishDate | 2020-11-01 |
publisher | BMC |
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series | Journal of Biomedical Science |
spelling | doaj.art-7d791233644e407588c6f294fa56885a2022-12-21T17:13:22ZengBMCJournal of Biomedical Science1423-01272020-11-0127111410.1186/s12929-020-00693-4MicroRNA-146a suppresses tumor malignancy via targeting vimentin in esophageal squamous cell carcinoma cells with lower fibronectin membrane assemblyHong-Yi Chang0Chi-Hua Lee1Yi-Syuan Li2Jing-Tong Huang3Sheng-Hui Lan4Yi-Fang Wang5Wu-Wei Lai6Yi-Ching Wang7Yan-Ju Lin8Hsiao-Sheng Liu9Hung-Chi Cheng10Department of Biotechnology and Food Technology, College of Engineering, Southern Taiwan University of Science and TechnologyDepartment of Microbiology and Immunology, College of Medicine, National Cheng Kung UniversityInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung UniversityInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung UniversityDepartment of Life Sciences and Institute of Genome Sciences, National Yang-Ming UniversityDepartment of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung UniversityDivision of Thoracic Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung UniversityInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung UniversityBiomedical Technology and Device Research Laboratories, Industrial Technology Research InstituteDepartment of Microbiology and Immunology, College of Medicine, National Cheng Kung UniversityInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung UniversityAbstract Background Esophageal squamous cell carcinoma (ESCC) is widely prevalent in Taiwan, and high metastatic spread of ESCC leads to poor survival rate. Fibronectin (FN) assembly on the cell membrane may induce ESCC mobility. MicroRNAs (MiRNAs) are abundant in and participate in tumorigenesis in many cancers. However, the role of MiRNA in FN assembly-related ESCC mobility remains unexplored. Methods We divided ESCC CE81T cells into high-FN assembly (CE81FN+) and low-FN assembly (CE81FN−) groups by flow cytometry. MiRNA microarray analysis identified miR-146a expression as the most down-regulated miRNA in comparison of CE81FN+ and CE81FN− cells. Results Cell proliferation and migration were decreased when CE81FN+ cells overexpressed transgenic miR-146a compared to the parental cells, indicating an inverse correlation between low miR-146a expression and high proliferation as well as motility of FN assembly ESCC cells. Furthermore, vimentin is the target gene of miR-146a involved in ESCC tumorigenesis. MiR-146a suppressed cell proliferation, migration and invasion of CE81FN+ cells through the inhibition of vimentin expression, as confirmed by real-time PCR, Western blotting and Transwell™ assay. Analysis of one hundred and thirty-six paired ESCC patient specimens revealed that low miR-146a and high vimentin levels were frequently detected in tumor, and that the former was associated with late tumor stages (III and IV). Notably, either low miR-146a expression or high vimentin level was significantly associated with poor overall survival rate among ESCC patients. Conclusions This is the first report to link FN assembly in the cell membrane with miR-146a, vimentin and ESCC tumorigenesis both in vitro and in ESCC patients.https://doi.org/10.1186/s12929-020-00693-4ESCCmiR-146aVimentinCell migrationInvasion |
spellingShingle | Hong-Yi Chang Chi-Hua Lee Yi-Syuan Li Jing-Tong Huang Sheng-Hui Lan Yi-Fang Wang Wu-Wei Lai Yi-Ching Wang Yan-Ju Lin Hsiao-Sheng Liu Hung-Chi Cheng MicroRNA-146a suppresses tumor malignancy via targeting vimentin in esophageal squamous cell carcinoma cells with lower fibronectin membrane assembly Journal of Biomedical Science ESCC miR-146a Vimentin Cell migration Invasion |
title | MicroRNA-146a suppresses tumor malignancy via targeting vimentin in esophageal squamous cell carcinoma cells with lower fibronectin membrane assembly |
title_full | MicroRNA-146a suppresses tumor malignancy via targeting vimentin in esophageal squamous cell carcinoma cells with lower fibronectin membrane assembly |
title_fullStr | MicroRNA-146a suppresses tumor malignancy via targeting vimentin in esophageal squamous cell carcinoma cells with lower fibronectin membrane assembly |
title_full_unstemmed | MicroRNA-146a suppresses tumor malignancy via targeting vimentin in esophageal squamous cell carcinoma cells with lower fibronectin membrane assembly |
title_short | MicroRNA-146a suppresses tumor malignancy via targeting vimentin in esophageal squamous cell carcinoma cells with lower fibronectin membrane assembly |
title_sort | microrna 146a suppresses tumor malignancy via targeting vimentin in esophageal squamous cell carcinoma cells with lower fibronectin membrane assembly |
topic | ESCC miR-146a Vimentin Cell migration Invasion |
url | https://doi.org/10.1186/s12929-020-00693-4 |
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