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.
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.
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DOI：
10.3892/or.2015.3909
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发表时间：
2015-06
期刊：
影响因子：
4.2
通讯作者：
L. Zheng;X. Jian;F. Guo;Ning Li;Canhua Jiang;Ping Yin;A. Min;Long Huang
中科院分区：
文献类型：
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作者：
L. Zheng;X. Jian;F. Guo;Ning Li;Canhua Jiang;Ping Yin;A. Min;Long Huang
口腔粘膜下纤维性变（OSF）是一种潜在的恶性疾病，主要见于亚洲人。槟榔与这种疾病有关。槟榔碱是槟榔生物碱之一，可诱导原代人口腔黏膜成纤维细胞产生上皮-间质转化（EMT）相关因子。然而，潜在的阿托伐他汀诱导的EMT在OSF的机制仍然未知。在本研究中，我们的目的是调查的作用microRNAs（miRNA）在阿托伐他汀诱导的HaCaT细胞EMT。我们发现miR-203在OSF组织中的表达较正常颊粘膜组织中显著下调，并且miR-203负调控分泌型卷曲相关蛋白4（SFRP 4），正调控跨膜-4 L六家族成员1（TM 4SF 1）。我们观察到，与载体对照细胞中的这些水平相比，miR-203的上调显著降低HaCaT细胞的细胞增殖，并显著上调细胞角蛋白19（CK 19）和E-cadherin蛋白的表达，而其显著下调N-cadherin和波形蛋白的表达。因此，我们提供的证据表明，miR-203在OSF的发病机制中发挥作用，这可能是OSF管理的目标。
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.