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miR-19a and miR-424 target TGFBR3 to promote epithelial-to-mesenchymal transition and migration of tongue squamous cell carcinoma cells.

Authors
  • Li, Duo1
  • Liu, Ke1
  • Li, Zhiyong1
  • Wang, Jian2
  • Wang, Xiaofeng1
  • 1 a Department of Oral and Maxillofacial Surgery , The Second Affiliated Hospital of Harbin Medical University , Harbin , China. , (China)
  • 2 b Department of Neurosurgery , The Fourth Affiliated Hospital of Harbin Medical University , Harbin , China. , (China)
Type
Published Article
Journal
Cell Adhesion & Migration
Publisher
Landes Bioscience
Publication Date
May 04, 2018
Volume
12
Issue
3
Pages
236–246
Identifiers
DOI: 10.1080/19336918.2017.1365992
PMID: 29130787
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Previous studies indicate that TGFBR3 (transforming growth factor type III receptor, also known as betaglycan), a novel suppressor of progression in certain cancers, is down-regulated in tongue squamous cell carcinoma (TSCC). However, the role of this factor as an upstream regulator in TSCC cells remains to be elucidated. The present study was designed to elucidate whether TGFBR3 gene expression is regulated by two microRNA molecules, miR-19a and miR-424. The study also aimed to determine if these microRNAs promote migration of CAL-27 human oral squamous cells. Immunohistochemistry (IHC) and western blot analyses demonstrated that TGFBR3 protein levels were dramatically down-regulated in clinical TSCC specimens. Conversely, bioinformatics analyses and qRT-PCR results confirmed that both miR-19a and miR-424 were markedly up-regulated in clinical TSCC specimens. In this study, we observed that transfection of a TGFBR3-containing plasmid dramatically inhibited epithelial-to-mesenchymal transition (EMT) and migration in CAL-27 cells. Co-immunoprecipitation analyses also revealed that TGFBR3 forms a complex with the β-arrestin 2 scaffolding protein and IκBα. Furthermore, overexpression of TGFBR3 decreased p-p65 expression and increased IκBα expression; these effects were subsequently abolished following knockdown of β-arrestin 2. Moreover, over-expression of miR-19a and miR-424 promoted migration and EMT in CAL-27 cells. We also observed that the promotion of EMT by miR-19a and miR-424 was mediated by the inhibition of TGFBR3. Our study provides evidence that miR-19a and miR-424 play important roles in the development of TSCC. These results expand our understanding of TGFBR3 gene expression and regulatory mechanisms pertaining to miRNAs.

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