Yuan Yao, Hou Xiaohui, Feng Hui, Liu Rui, Xu Hao, Gong Wang, Deng Jing, Sun Chongkui, Gao Yijun, Peng Jieying, Wu Yingfang, Li Jiang, Fang Changyun, Chen Qianming
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu China, 610041.
Laboratory of Oral Biomedical Science and Translational Medicine, School of Stomatology, Tongji University, Shanghai China, 200072.
Oncotarget. 2016 Sep 13;7(37):60348-60365. doi: 10.18632/oncotarget.11254.
Oral submucous fibrosis (OSF) is a pre-cancerous lesion, which is characterized by fibrosis of the oral submucosa. Despite large body of studies focusing on this disease, the molecular mechanisms underlying the progression of OSF remained unclear. In this study, 2-DE-based proteomic approaches were employed to identify the differently expressed proteins between OSF and normal tissues. In total, 88 proteins were identified with altered expression levels, including CypA. Upregulation of CypA was further validated through immunohistochemistry staining combined with Q-PCR and western blot by using clinical samples. Statistical analyses reveal that CypA expression level is correlated to the progression of OSF. Finally, functional study reveals a pro-proliferative property of CypA in fibroblast cells by using multiple in vitro models. The present data suggest that CypA might be a potential biomarker and therapeutic target for OSF, and will lead to a better understanding of OSF pathogenesis.
口腔黏膜下纤维化(OSF)是一种癌前病变,其特征为口腔黏膜下层的纤维化。尽管大量研究聚焦于该疾病,但OSF进展的分子机制仍不清楚。在本研究中,采用基于二维电泳的蛋白质组学方法来鉴定OSF组织与正常组织之间差异表达的蛋白质。总共鉴定出88种表达水平改变的蛋白质,包括环孢素A(CypA)。通过免疫组织化学染色结合Q-PCR和蛋白质印迹法,利用临床样本进一步验证了CypA的上调。统计分析表明,CypA表达水平与OSF的进展相关。最后,通过多种体外模型进行的功能研究揭示了CypA在成纤维细胞中的促增殖特性。目前的数据表明,CypA可能是OSF的潜在生物标志物和治疗靶点,这将有助于更好地理解OSF的发病机制。