POLE2 Regulates Apoptosis of Oral Squamous Cell Carcinoma Cells through the PI3K/AKT Signaling Pathway.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck, but its occurrence and progression mechanisms remain unclear. In addition-there is a lack of effective targeting drugs. The second major subunit of DNA polymerase (POLE2) catalyzes the prolongation of new strand replication and modifies exonuclease domain activity. Our previous study found that POLE2 was associated with OSCC progression, but the mechanism remains unclear. METHODS: The expression of POLE2 in OSCC tissues was detected using immunological assays. Mann-Whitney U analysis was used to investigate the relationship between POLE2 gene expression and tumor classification and prognosis of OSCC. POLE2 expression was inhibited in OSCC cells, and the effects of gene and protein expression were detected using RT-PCR and Western blotting. The POLE2 knockout model was constructed by transfecting a lentiviral vector. Cell proliferation, apoptosis, and migration were detected using various assays including colony formation, MTT, flow cytometry, wound healing assay, Transwell assay, and the Human Apoptosis Antibody Array. The animal model of OSCC was established by subcutaneous injection of transfected HN6 into 4-week-old female nude mice. After 30 days, tumors were removed under anesthesia and tumor weight and dimension were recorded. Tumor cell proliferation was analyzed using Ki67 staining. RESULTS: POLE2 gene levels were significantly higher in the OSCC tissues than in the normal tissues. In addition, POLE2 gene levels were statistically correlated with tumor classification and prognosis. Silencing POLE2 inhibited the proliferation of oral cancer cells and promoted apoptosis in vitro. Animal experiments also supported a positive correlation between POLE2 and OSCC tumor formation. We further demonstrated that POLE2 could upregulate the expression of apoptosis-related proteins such as caspase-3, CD40, CD40L, DR6, Fas, IGFBP-6, p21, and SMAC. In addition, POLE2 regulated OSCC development by inhibiting the PI3K/AKT signaling pathway. CONCLUSION: POLE2 is closely related to the progression of OSCC. Thus, POLE2 may be a potential target for OSCC treatment.

[Identification of circular RNA expression profiles in oral lichen planus].

PURPOSE: To construct the expression profile of circular RNA (circRNA) in human oral lichen planus (OLP), and to identify and validate the differentially expressed circRNA in oral lichen planus tissues and provide theoretical basis for the diagnosis and treatment of this disease. METHODS: Six patients newly diagnosed with OLP from September to December 2018 in the Department of Oral Mucosal Diseases, Shanghai Ninth People's Hospital and 6 healthy volunteers were enrolled in this study. RNA sequencing and evaluation in OLP tissues and normal oral mucosa were performed by high-throughput RNA sequencing technology, and the differences between groups were analyzed. qRT-PCR was used to validate the results. Statistical analysis was conducted with SPSS 24.0 software package. Finally, bioinformatics techniques GO (Gene Ontology) enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway were used to analyze the functions and related pathways of the dysregulated genes. RESULTS: According to the sequencing results, 85 differentially expressed circRNAs with fold change > 2 were identified in OLP tissues compared to the normal oral mucosa, including 66 upregulated circRNAs and 19 downregulated circRNAs. Three circRNAs with the most significant up-regulation and down-regulation were selected for qRT-PCR verification in expanded samples, and the results were consistent with the sequencing results. Bioinformatics analysis suggested that the differentially expressed circRNAs may play an important role in the occurrence and progression of oral lichen planus. CONCLUSIONS: Differentially expressed circRNAs between oral lichen planus tissues and normal oral mucosa were identified, which may be involved in the pathogenic mechanism of oral lichen planus and could be potential biomarkers for diagnosis and treatment of this disease.

A retrospective clinicopathological study on oral lichen planus and malignant transformation: Analysis of 518 cases

Objective: To investigate the epidemiological and clinical characteristics of a relatively large cohort of patients with oral lichen planus (OLP) from eastern China. Study design: A total of 518 patients with histologically confirmed OLP in a long-term follow-up period (6 months-21.5 years) were retrospectively reviewed in our clinic. Results: Of the 518 patients, 353 females and 165 males were identified. The average age at diagnosis was 46.3 years (range 9-81 years) with the buccal mucosa being the most common site (87.8%). At initial presentation, white lichen and red lichen was seen in 52.3% and 47.7% patients, respectively. Of these, 5 (0.96%) patients previously diagnosed clinically and histopathologically as OLP developed oral cancer. All of them were the females with no a history of smoking or alcohol use. Conclusions: Clinical features of eastern Chinese OLP patients were elucidated. Notably, approximately 1% of OLP developed into cancer, which provides further evidence of potentially malignant nature of OLP (AU)

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A retrospective clinicopathological study on oral lichen planus and malignant transformation: analysis of 518 cases.

OBJECTIVE: To investigate the epidemiological and clinical characteristics of a relatively large cohort of patients with oral lichen planus (OLP) from eastern China. STUDY DESIGN: A total of 518 patients with histologically confirmed OLP in a long-term follow-up period (6 months-21.5 years) were retrospectively reviewed in our clinic. RESULTS: Of the 518 patients, 353 females and 165 males were identified. The average age at diagnosis was 46.3 years (range 9-81 years) with the buccal mucosa being the most common site (87.8%). At initial presentation, white lichen and red lichen was seen in 52.3% and 47.7% patients, respectively. Of these, 5 (0.96%) patients previously diagnosed clinically and histopathologically as OLP developed oral cancer. All of them were the females with no a history of smoking or alcohol use. CONCLUSIONS: Clinical features of eastern Chinese OLP patients were elucidated. Notably, approximately 1% of OLP developed into cancer, which provides further evidence of potentially malignant nature of OLP.

Malignant potential of oral and labial chronic discoid lupus erythematosus: a clinicopathological study of 87 cases.

AIMS: To investigate clinicopathological features and identify clinicopathological risk factors for the malignant transformation of oral and labial chronic discoid lupus erythematosus (DLE) in a relatively large number of patients from China. METHODS AND RESULTS: A total of 87 patients with clinical and histopathological diagnosis of DLE between 1993 and 2009 were reviewed retrospectively in our hospital. The average age at diagnosis was 51.7 years, with a male:female ratio of 1:1.8. The lower lip was the most common site (71.3%). We documented six DLE patients with malignant transformation. On univariate analysis, patients with high-risk dysplasia (P = 0.002) or aged >60 (P = 0.045) were associated with DLE malignant transformation, but gender, lesion site, smoking and alcohol intake were not risk factors. On multivariate analysis, high-risk dysplasia was a significant indicator for DLE malignant transformation. High-risk dysplasia was associated with a 14.24-fold [95% confidence interval (95% CI), 1.97-102.88; P = 0.008] increased risk of malignant transformation, compared with non/low-risk dysplasia. CONCLUSIONS: The utilization of high-risk dysplasia as a significant indicator for evaluating malignant transformation risk in patients with DLE is suggested, which may be helpful to guide treatment selection.

Squamous cell carcinoma development in previously diagnosed oral lichen planus: de novo or transformation?

OBJECTIVES: The objectives of this study were to investigate the incidence of oral squamous cell carcinoma (OSCC) developing in lesions that were previously diagnosed as oral lichen planus (OLP), and to evaluate potential contributing factors that might be associated with an increased risk for the development of OSCC in these patients. STUDY DESIGN: We retrospectively reviewed a relatively large cohort of 518 patients with OLP who received long-term follow-up (range, 6 months-21.5 years). RESULTS: There were 353 females and 165 males. Of these, 5 (0.96%) patients developed OSCC with a mean duration of 70 months. All were females with no history of smoking or alcohol use. Four of them received corticosteroid therapy. Notably, 1 of these patients received systemic corticosteroid therapy 13 months before transformation, and died of metastatic disease 46 months after transformation. CONCLUSIONS: The incidence of OSCC developing in lesions previously diagnosed as OLP is less than 1%, and females were more commonly affected. These cases appear to represent the transformation of OLP into OSCC, however it cannot be entirely ruled out that these cases may represent de novo OSCC.

Oral melanotic macule and primary oral malignant melanoma: epidemiology, location involved, and clinical implications.

BACKGROUND: Oral malignant melanoma must be differentiated from melanotic macule. STUDY DESIGN: Retrospective review of 2 series of oral melanotic macule (n = 52) and oral melanoma (n = 130) were conducted to investigate the epidemiology and location involved and assess their differences. RESULTS: The mean age of oral melanotic macule patients was 47.3 years, with female:male ratio 2.1 and the lower lip being the predominant location. The mean age of oral melanoma patients was 53.8 years, with no observed sex predilection and the main locations being palate and gingiva. Differences between the 2 cohorts in age (P = .006), gender (P = .014), and lesion site (P < .001) were noted. In this review, 1 case of oral melanotic macule was found to subsequently develop into melanoma. CONCLUSIONS: Oral melanotic macule may possess malignant potential. Biopsy is recommended to differentiate oral melanoma from melanotic macule for male patients >60 years old with suspected melanotic macule lesion located on the palate.

A population-based study of acquired bilateral nevus-of-Ota-like macules in Shanghai, China.

Acquired bilateral nevus-of-Ota-like macule (ABNOM) is a common skin dyspigmentation in Asian females. Although its clinical characteristics are well defined, its epidemiology and pathogenesis remain unclear. A large population-based cross-sectional study was conducted to determine the prevalence and risk factors of ABNOM. A total of 8,680 subjects (ages ranging from newborn to 99 years old; 54% female) were selected from urban areas in Shanghai, China, using a multistage sampling method. All participants (response rate=97%) were interviewed and examined for the presence of various pigmentary disorders by board-certified dermatologists. ABNOM was found in 2.5% of the study population (0.5% of males and 4.2% of females), and 90% of cases observed were female. In females, prevalence rose after the age of 15 years and sharply declined after the age of 50 years, with nearly half of the cases observed within ages 45-55 years (prevalence=8.5%). Age, contraceptive use, and sun exposure were independently associated with ABNOM. Women with ABNOM were less likely to have facial nevomelanocytic nevi and seborrheic keratoses. These findings indicate that sex hormone alteration and UV exposure may independently have an important role on the pathogenesis of ABNOM.

Chemical analysis of Hericium erinaceum polysaccharides and effect of the polysaccharides on derma antioxidant enzymes, MMP-1 and TIMP-1 activities.

Hericium erinaceum was a traditional edible mushroom in Asia. In this study, we extracted polysaccharides from H. erinaceum. HPLC analysis indicated that H. erinaceum polysaccharides were mainly composed of glucose and galactose. The FT-IR spectra of H. erinaceum polysaccharides showed characteristic absorption bands of polysaccharides. The pharmacological properties of H. erinaceum polysaccharides were investigated in aged rats. Results showed that H. erinaceum polysaccharides significantly enhanced skin antioxidant enzymes, MMP-1, TIMP-1 activities and collagen protein levels in a dose-dependent manner. It can be concluded that H. erinaceum polysaccharides possess anti-skin-aging activities.