miR-203 inhibits arecoline-induced epithelial‑mesenchymal transition by regulating secreted frizzled-related protein 4 and transmembrane-4 L six family member 1 in oral submucous fibrosis

Zheng,Lian; Jian,Xinchun; Guo,Feng; Li,Ning; Jiang,Canhua; Yin,Ping; Min,An-Jie; Huang,Long

doi:10.3892/or.2015.3909

miR-203 inhibits arecoline-induced epithelial‑mesenchymal transition by regulating secreted frizzled-related protein 4 and transmembrane-4 L six family member 1 in oral submucous fibrosis

Authors:
- Lian Zheng
- Xinchun Jian
- Feng Guo
- Ning Li
- Canhua Jiang
- Ping Yin
- An-Jie Min
- Long Huang
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Affiliations: Department of Oral and Maxillofacial Surgery, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China
Published online on: April 9, 2015 https://doi.org/10.3892/or.2015.3909
Pages: 2753-2760

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Abstract

Oral submucous fibrosis (OSF) is a potentially malignant disease predominantly found in Asian people. The areca nut has been implicated in this disease. Arecoline, one of the areca alkaloids, induces epithelial-mesenchymal transition (EMT)-related factors in primary human buccal mucosal fibroblasts. Yet, the mechanisms of the underlying arecoline-induced EMT in OSF remain unknown. In the present study, we aimed to investigate the role of microRNAs (miRNAs) in arecoline-induced EMT in HaCaT cells. We found that miR-203 was significantly downregulated in OSF tissues compared to that in normal buccal mucosa tissues, and that miR-203 negatively regulated secreted frizzled-related protein 4 (SFRP4) and positively regulated transmembrane-4 L six family member 1 (TM4SF1). We observed that upregulation of miR-203 significantly decreased the cell proliferation of HaCaT cells, and significantly upregulated the expression of cytokeratin 19 (CK19) and E-cadherin proteins, whereas it significantly downregulated the expression of N-cadherin and vimentin compared to these levels in the vehicle control cells. Thus, we provide evidence to illustrate that miR-203 plays a role in the pathogenesis of OSF, which may be a target for OSF management.

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