Molecular pathways of oral submucous fibrosis and its progression to malignancy

Abstract

Objective: The review aims to comprehend various factors engaged in the alteration of molecular events resulting in Oral submucous fibrosis (OSMF) and its malignant transformation.

Design: Literature pertinent to pathways involved in OSMF were explored in databases such as PubMed, Scopus and Google Scholar. The relevant literature was reviewed and critically appraised in this narrative review.

Results: Areca nut components influence myriad of cellular molecules such as cytokines, growth factors, myofibroblasts, non-coding RNAs and alter their expression. These aberrantly expressed molecules drive the progression of OSMF from localized inflammation to fibrosis of buccal mucosa. The oral tissue suffers from oxidative stress, hypoxia, autophagy, aberration of cell cycle and DNA damage. Apoptosis of epithelial layer results in its atrophy facilitating deeper penetration of areca nut elements. With the advance of disease, epithelial-mesenchymal transition eventuates and promotes dysplasia. The jeopardized expression of various cellular molecules, suppressed apoptosis, along with increased genetic alterations and neovascularization favors the malignant transformation.

Conclusion: OSMF is a progressive disorder with complex mechanism of pathogenesis initiated by inflammation of oral mucosa. Continuous habit of areca nut chewing and the resulting insult to the tissues prevents healing process and is destined to debilitating disease which affects the quality of life with a higher probability of progression to malignancy.

Keywords: Cell cycle regulation; DNA Double strand breaks; DNA methylation; Epithelial mesenchymal transition; Oral submucous fibrosis; Oxidative stress.