MicroRNA-146a suppresses tumor malignancy via targeting vimentin in esophageal squamous cell carcinoma cells with lower
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RESEARCH
MicroRNA‑146a suppresses tumor malignancy via targeting vimentin in esophageal squamous cell carcinoma cells with lower fibronectin membrane assembly Hong‑Yi Chang1†, Chi‑Hua Lee2†, Yi‑Syuan Li3,5†, Jing‑Tong Huang3, Sheng‑Hui Lan4, Yi‑Fang Wang5, Wu‑Wei Lai6, Yi‑Ching Wang3,7, Yan‑Ju Lin8, Hsiao‑Sheng Liu2,3,9,10* and Hung‑Chi Cheng3,5*
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. Micro‑ RNAs (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 prolif‑ eration 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 C E81FN+ 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. Keywords: ESCC, miR-146a, Vimentin, Cell migration, Invasion
*Correspondence: [email protected]; [email protected] † Hong-Yi Chang, Chi-Hua Lee and Yi-Syuan Li equal contribution 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 Full list of author information is available at the end of the article
Background Esophageal cancer is the fifth most common cancer in males and the ninth leading cause of cancer death in Taiwan [1]. Two major histological types of esophageal cancers are esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EA). Over 95% of predominant esophageal cancers in Taiwan are classified as ESCC and its incidence continues to increase [2].
© The Author(s) 2020. Open Access This article is licensed under a Creative Comm
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