Aberrant SSEA-4 upregulation mediates myofibroblast activity to promote pre-cancerous oral submucous fibrosis

Yu, Cheng–Chia; Yu, Chuan‐Hang; Chang, Yu‐Chao

doi:10.1038/srep37004

Cited by 38 publications

(28 citation statements)

References 39 publications

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“…Myofibroblast can be formed by transdifferentiation of oral keratinocytes activated by arecoline. A study demonstrated that the expression of stage-specific embryonic antigen-4 (SSEA-4, a sialyl-glycolipid) induced by arecoline in buccal mucosal fibroblasts was significantly increased in AN chewing-associated OSF tissues.Knockdown of SSEA-4 synthesis might abolish MFB activity in fibrotic buccal mucosal fibroblasts 21.…”

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confidence: 99%

Oral submucous fibrosis in Asian countries

Peng

Chen

et al. 2019

J Oral Pathology Medicine

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Oral submucous fibrosis (OSF) is a chronic, insidious, and progressive oral mucosal disease that affects entire oral cavity and sometimes pharynx. It is precancerous and characterized by blanching and burning sensation of oral mucosa, staining of teeth and gingiva, and restricted mouth opening. It is multifactorial with a high incidence in chewers of areca nut (AN). This oral potentially malignant disorder has a high rate of malignant transformation rate (7%-30%) to oral squamous cell carcinoma (OSCC). 1 It is prevalent in Asian countries and has spread in Europe and North America. The prevalence of OSF was reported to be 1.0%-3.03% in Hunan Province, mainland China, 2 0.15%-14.4% in Vietnam, 3 and 0.086%-17.6% in Taiwan. 4 In the past decades, many efforts have been devoted to etiology, pathogenesis, and treatment of OSF. However, the research progress is still unsatisfactory. For instance, the etiology of OSF is commonly attributed to AN chewing, but some OSF patients did not have the habit. Also, there is no staging or grading scheme universally accepted and employed by clinicians, pathologists, and surgeons. Moreover, the pathogenesis and mechanism of OSF transformation into carcinomas are still obscure. Undoubtedly, it is crucial to make further studies of OSF to fill in the gaps. This article, for the first time, provided a detailed review of research advances of OSF in Asian countries, based on a comprehensive literature search using several primary databases (Figure 1), in which the terminologies, for example, OSF and oral potential malignant diseases (OPMD), were used. The OSF's etiology, histopathology, pathogenesis, clinical manifestations, diagnosis and differential diagnosis, and treatments were reviewed. The main challenges and corresponding measures were also discussed for guiding clinical research and practice concerning the disease. | E TI O LO GYOral submucous fibrosis is characterized by its multifactorial etiology. The most commonly identified factors include AN chewing, nutritional disorders, and genetic predisposition. They act individually or synergistically in the development of OSF. AbstractOral submucous fibrosis (OSF) is a chronic, insidious, and progressive oral mucosal disease that affects entire oral cavity and sometimes pharynx. This oral potentially malignant disorder has a high rate of malignant transformation (7%-30%) to oral squamous cell carcinoma (OSCC), posing global problems for public health. Due to enormous efforts dedicated to this disease in the past decades, there have been significant advances in identification of its etiology and pathogenesis as well as development of corresponding therapeutic approaches, in spite of several challenges. This study reviewed the existing literature concerning OSF in Asian countries, encompassing its etiology, histopathology, pathogenesis, clinical manifestations, diagnosis and differential diagnosis, and treatments. For improving treatment of OSF, the multifactorial etiology analysis, incorporation of effective molecular pathways, cy...

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confidence: 99%

Oral submucous fibrosis in Asian countries

Peng

Chen

et al. 2019

J Oral Pathology Medicine

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“…Thirteen studies included normal oral mucosa for comparison, whereas two studies included fibrous hyperplasia with normal epithelium and one study included hyperkeratosis. Three studies detected myofibroblasts in the stroma of the normal oral mucosa (Angadi, Kale, & Hallikerimath, ; Sarode, Sarode, Deshmukh, Raktade, & Patil, ; Yu, Yu, & Chang, ). Of 189 normal oral mucosa samples, 20 (10.6%) samples were positive for myofibroblasts, 16 showing scarce cells and four with an abundant number of cells.…”

Section: Resultsmentioning

confidence: 99%

“…In OSMF, of 213 cases from six studies, 188 (88.3%) were positive for myofibroblasts. Four studies (Angadi et al., ; Gupta, Metgud, & Gupta, ; Sarode et al., ; Yu et al., ) demonstrated that the presence of myofibroblasts is significantly higher in OSMF compared with normal oral mucosa. A statistical significance was also noted between advanced OSMF (cases with dysplasia) compared to early OSMF (cases without dysplasia), as reported by Angadi et al.…”

Section: Resultsmentioning

confidence: 99%

Myofibroblasts in oral potentially malignant disorders: Is it related to malignant transformation?

Coletta

Salo

2018

Oral Diseases

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In oral cancer, acquisition of α-smooth muscle actin (α-SMA)-positive fibroblasts, known as myofibroblasts or carcinoma-associated fibroblasts (CAF), is an important event for progression and metastasis. However, the contribution of myofibroblasts in oral potentially malignant disorders (OPMD) remains controversial. This systematic review provides evidence that immunodetection of myofibroblasts may identify oral submucous fibrosis (OSMF) with high risk of malignant transformation, but does not represent an auxiliary tool to predict the malignant potential of leukoplakia and erythroplakia, the most common OPMD.

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“…Primary normal buccal mucosa fibroblasts (BMFs) and fibrotic buccal mucosa fibroblasts (fBMFs) were isolated from normal human buccal oral mucosa and OSF lesions, respectively, with written informed consent from patients. These patient-derived fBMFs exhibited myofibroblasts characteristics and have been used in several studies [6,31]. Cells were cultured as previously described [6], and passaged routinely at 90% confluence.…”

Section: Cell Culture For Buccal Mucosa Fibroblasts (Bmfs) and Fibrotmentioning

confidence: 99%

LINC00312/YBX1 Axis Regulates Myofibroblast Activities in Oral Submucous Fibrosis

Chen

Fang

et al. 2020

IJMS

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Oral submucous fibrosis (OSF) has been recognized as a precancerous disorder in the oral cavity. Great effort has been made to inhibit the malignant progression of OSF over the past decades, but the cure of this fibrosis disease has not been discovered. In the present study, we found that a long noncoding RNA, LINC00312, was upregulated in OSF tissues, and positively associated with several fibrosis factors, such as α-SMA, type I collagen, and fibronectin. As such, we sought to investigate the role of LINC00312 in OSF progression and identify its interacting factor that mediated oral fibrogenesis. Our results showed that the inhibition of LINC00312 downregulated the myofibroblast activities, including collagen gel contractility, transwell migration, and wound healing, as well as the gene expression of myofibroblast markers. We verified that YBX1 was a downstream factor of LINC00312 and revealed that the downregulation of YBX1 repressed the gene expression of α-SMA and p-Smad2 along with the reduced myofibroblast phenotypes. Most importantly, we demonstrated that the LINC00312-induced myofibroblast activities were reverted by the knockdown of YBX1, suggesting that the LINC00312-mediated myofibroblast transdifferentiation was through YBX1. Collectively, our findings revealed that the LINC00312/ YBX1 axis may serve as a target for the development of therapies against OSF.

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Aberrant SSEA-4 upregulation mediates myofibroblast activity to promote pre-cancerous oral submucous fibrosis

Cited by 38 publications

References 39 publications

Oral submucous fibrosis in Asian countries

Oral submucous fibrosis in Asian countries

Myofibroblasts in oral potentially malignant disorders: Is it related to malignant transformation?

LINC00312/YBX1 Axis Regulates Myofibroblast Activities in Oral Submucous Fibrosis

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