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MicroRNA-328 inhibits migration and epithelial–mesenchymal transition by targeting CD44 in nasopharyngeal carcinoma cells

Authors Lin CH, Chiang MC, Chen YJ

Received 14 September 2017

Accepted for publication 14 February 2018

Published 27 April 2018 Volume 2018:11 Pages 2375—2385

DOI https://doi.org/10.2147/OTT.S151665

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Jianmin Xu


Chien-Hung Lin,1,2 Ming-Chang Chiang,3 Yann-Jang Chen1,4,5

1Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; 2Department of Pediatrics, Zhongxing Branch, Taipei City Hospital, Taipei, Taiwan; 3Department of Life Science, College of Science and Engineering, Fu Jen Catholic University, New Taipei City, Taiwan; 4Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan; 5Department of Pediatrics, Renai Branch, Taipei City Hospital, Taipei, Taiwan

Background: MicroRNAs (miRNAs) play crucial roles in various types of cancers, particularly in tumor development, migration, and progression. Dysregulation of miR-328 was reported to occur in some types of human malignancies, however, the role of miR-328 in nasopharyngeal carcinoma (NPC) and its potential involvement in metastasis remain undetermined.
Methods: The invasion capacity of NPC sphere-forming cells was evaluated by in vitro cell migration assays. Differential miRNAs expression was examined in NPC sphere-forming cells compared to parental monolayer cells using miRNA array analysis. The role of miR-328 in regulating NPC cells migratory properties was analyzed after miR-328 mimics transfection. The expression of E-cadherin and CD44 was analyzed by flow cytometry. CD44 was examined as a target of miR-328 through luciferase reporter assays and Western blotting.
Results: Here, we report that NPC TW01 and TW06 sphere-forming cells exhibited increased migratory ability in comparison with parental monolayer cells. Sphere-forming cells had significantly lower levels of miR-328, as observed using miRNA arrays and confirmed through real-time polymerase chain reaction. Overexpression of miR-328 induced by transfection with synthetic miR-328 mimics decreased the migration of NPC sphere-forming cells. The inhibitory effects were associated with increased expression of E-cadherin and the downregulated expression of mesenchymal markers such as N-cadherin, Snail, and vimentin. Moreover, our results demonstrated that miR-328 suppressed NPC cell migration and inhibited the epithelial–mesenchymal transition process directly through a binding site on the CD44 3′ untranslated region.
Conclusion: miR-328, a previously unrecognized miRNA, may serve as a potential prognostic marker and therapeutic target for NPC.

Keywords: miR-328, EMT, CD44, NPC, cancer cell migration

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