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Review
. 2023 Mar 5;24(5):4992.
doi: 10.3390/ijms24054992.

Oral Submucous Fibrosis: Etiological Mechanism, Malignant Transformation, Therapeutic Approaches and Targets

Xiaofeng Qin  1 , Yujie Ning  1 , Liming Zhou  1 , Youming Zhu  1
Affiliations
Review

Oral Submucous Fibrosis: Etiological Mechanism, Malignant Transformation, Therapeutic Approaches and Targets

Xiaofeng Qin et al. Int J Mol Sci. .

Abstract

Oral submucosal fibrosis (OSF) is a chronic, progressive and potentially malignant oral disorder with a high regional incidence and malignant rate. With the development of the disease, the normal oral function and social life of patients are seriously affected. This review mainly introduces the various pathogenic factors and mechanisms of OSF, the mechanism of malignant transformation into oral squamous cell carcinoma (OSCC), and the existing treatment methods and new therapeutic targets and drugs. This paper summarizes the key molecules in the pathogenic and malignant mechanism of OSF, the miRNAs and lncRNAs with abnormal changes, and the natural compounds with therapeutic effects, which provides new molecular targets and further research directions for the prevention and treatment of OSF.

Keywords: epithelial–mesenchymal transition; lncRNAs; malignant transformation; miRNAs; myofibroblast; natural compounds; oral squamous cell carcinoma; oral submucous fibrosis.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
A multi-factor pathogenic model of OSF with BQ as the main cause. Firstly, BQ components can play a pathogenic role in conjunction with tobacco and alcohol, vitamin and trace element abnormalities, immune factors and genetic susceptibility, and directly stimulate keratinocytes and fibroblasts and cause ulcers, inflammation, oxidative stress, cell senescence, cytotoxicity, epithelial atrophy, etc. Secondly, the above factors can also increase collagen synthesis, collagen cross-linking, reduce collagen degradation, fibroblast–myofibroblast differentiation and activation by regulating TGF-β, ROS, LOX, MMPs, TIMPs, PAI-1, Cystatin C, HIF-1α, ncRNAs and other signal molecules. Fibrosis leads to vascular occlusion, reduced blood supply and hypoxia, aggravating the vicious cycle of OSF and making fibrosis even more irreversible.
Figure 2
Figure 2
Model of malignant transformation based on OSF. BQ and its carcinogenic components (areca alkaloids, hydrated lime, nitrosamines, polyphenols, etc.), the senescence of fibroblasts, EMT, the continuous production of ROS, the aggravation of hypoxia, the continuous inflammatory environment and the aggravation of fibrosis will lead to malignant transformation through the regulation of TGF-β, HIF-1α, NF-κB, Notch, STAT3, IGF-1R and other pathways and cytokines on the basis of OSF. This will lead to the generation of cancer stem cells, affect cell growth, migration, invasion, metabolism, and even resistance to chemotherapy and radiotherapy, and promote the occurrence and progression of OSCC on the basis of OSF.
Figure 3
Figure 3
The important molecules and processes involved in OSF pathogenesis and malignant transformation into OSCC.
See this image and copyright information in PMC

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