Nicotine promotes the development of oral leukoplakia via regulating peroxiredoxin 1 and its binding proteins

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.

<i>SERPINE1</i> as an Independent Prognostic Marker and Therapeutic Target for Nicotine-Related Oral Carcinoma

“…A r t i c l e species production; however, aberrant expressions of some genes, such as CoQ (10), can increase the resistance of oral cancer cells to Bleomycin [26]. Docetaxel has been used in first-line chemotherapy for HNC, as well as in the treatment of recurrent and metastatic HNC.…”

“…For example, nicotine exposure can elevate the expression of α5 nicotinic acetylcholine receptors and survivin in lung cells, which plays an important role in the occurrence and development of lung adenocarcinoma [ 9 ]. Nicotine exposure can also induce the abnormal expression of PRX1 and the genes encoding for its interacting proteins CFL1 and PPP2R1A , thereby promoting the transformation of normal oral cells into cancer cells [ 10 ]. However, most of the literature has focused on single genes or pathways, which may lead to biases in our understanding of nicotine’s oncogenic mechanisms.…”