- 作者: 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 and Hung-Chi Cheng
- 作者服務機構: 1. Department of Biotechnology and Food Technology, College of Engineering, Southern Taiwan University of Science and Technology, Tainan, Taiwan 2. Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 3. Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan 4. Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 5. Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan 6. Division of Thoracic Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan 7. Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 8. Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan 9. M. Sc. Program in Tropical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 10. Center for Cancer Research, Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- 中文摘要:
- 英文摘要:
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. - 中文關鍵字:
- 英文關鍵字: ESCC, miR-146a, Vimentin, Cell migration, Invasion