Abstract
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.
Highlights
Oral submucous fibrosis (OSF) is a chronic precancerous oral lesion that mainly occurs in Asia
Despite large body of studies focusing on this disease, the molecular mechanisms underlying the progression of OSF remained unclear
Inhibition of CypA by siRNAs or chemical antagonist induced marked apoptosis in these cells. These findings suggest that CypA is a key regulator of fibroblast viability, and contribute to OSF development probably via promoting fibroblast cell proliferation
Summary
Oral submucous fibrosis (OSF) is a chronic precancerous oral lesion that mainly occurs in Asia. Most OSF patients suffered from spicy sensitivity, difficulties in mouth opening or tough movement, and stiffness of oral mucous [1]. Parts of OSF patients may develop into oral carcinoma. Epidemiological study has shown that the malignant transformation rate of OSF patients is 2%-12% [2]. It has been noted that the incidence of OSF in those areas where people have the habit of chewing areca nut is markedly higher than other regions [4]. The main harmful chemical in the areca nut, arecoline, can induce cytotoxicity in human buccal mucosa and causes the fibrosis lesion [5]. In spite of a large body of studies focusing on the etiology and pathogenesis of OSF, the molecular mechanisms of this disease are still not fully understood
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