Abstract
Tobacco can induce reactive oxygen species (ROS) production extensively in cells, which is a major risk factor for oral leukoplakia (OLK) development. Peroxiredoxin 1 (Prx1) is a key antioxidant protein, upregulated in a variety of malignant tumors. We previously found that nicotine, the main ingredient of tobacco, promotes oral carcinogenesis via regulating Prx1. The aim of the present study was to screen and identify the Prx1 interacting proteins and investigate the mechanisms of nicotine on the development of OLK. Through liquid chromatography-tandem mass spectrometry combined with bioinformatics analysis, the candidate Prx1 interacting proteins of cofilin-1 (CFL1), tropomyosin alpha-3 chain (TPM3), and serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform (PPP2R1A) were screened in human dysplastic oral keratinocyte cells treated with nicotine. CFL1, TPM3, and PPP2R1A were highly expressed in human OLK tissues. The expression of CFL1 increased and the expression of PPP2R1A decreased in OLK of smokers compared to that in OLK of non-smokers. Nicotine upregulated CFL1 and downregulated PPP2R1A in 4-nitro-quinoline-1-oxide (4NQO)-induced OLK tissues in mice in part dependent on Prx1. Furthermore, the in-situ interaction of CFL1, TPM3, and PPP2R1A with Prx1 were validated in human OLK tissues. Our results suggested that tobacco might promote the development of OLK via regulating Prx1 and its interacting proteins CFL1 and PPP2R1A.
Highlights
Tobacco is the major risk factor associated with oral leukoplakia (OLK) malignant transformation, which has an effect of promoting generation of reactive oxygen species (ROS) and causing oxidative damage to the oral mucosa [1,2]
Nicotine upregulated the expression of Peroxiredoxin 1 (Prx1) in oral precancerous lesion dysplastic oral keratinocyte (DOK) and oral squamous cell carcinoma (OSCC) cells and promoted the development of oral precancerous lesions by regulating Prx1 expression involved in cell proliferation and apoptosis [7,8]
Cell proliferation is a vital indicator for understanding the mechanisms of function of certain genes, proteins, and pathways involved in cell survival and death
Summary
Tobacco is the major risk factor associated with oral leukoplakia (OLK) malignant transformation, which has an effect of promoting generation of reactive oxygen species (ROS) and causing oxidative damage to the oral mucosa [1,2]. As the main addictive component of tobacco, nicotine affects tumorigenesis by regulation of cell survival, apoptosis, proliferation, metastasis, angiogenesis, and immunosurveillance [3]. Nicotine upregulated the expression of Prx in oral precancerous lesion dysplastic oral keratinocyte (DOK) and OSCC cells and promoted the development of oral precancerous lesions by regulating Prx expression involved in cell proliferation and apoptosis [7,8]. These results suggest that tobacco might promote the development of OLK by regulating Prx. Extensive research is necessary to elucidate the molecular function of Prx in tobacco-related OLK
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Schedule a callMore From: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
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