RESUMO
Oral lichen planus (OLP) is a common oral mucosal disease, which is generally considered a potentially malignant lesion. To identify efficiently prognostic biomarker, we investigated the microRNA-137 (miR-137) promoter methylation in OLP and compared with the samples from healthy volunteers and patients with oral squamous cell carcinoma (OSCC). A total of 20 OLP and 12 patients with OSCC as well as 10 healthy subjects were subjected to miR-137 promoter methylation analysis using methylation-specific PCR (MSP). To address the malignancy prediction potential from miR-137 promoter methylation status, methylation of the p16 gene, a well-known tumor suppressor, was investigated in the same samples. The p16 methylation and miR-137 promoter methylation were found to be 25% and 35% in patients with OLP, 50% and 58.3% in patients with OSCC, and 0% and 0% in healthy subjects, respectively. The differences between miR-137 and p16 methylation levels were statistically significant between healthy controls and patients. Methylation levels of the two promoters were also influenced by age, gender, and lesion duration. Interestingly, aberrant promoter methylation of the p16 and miR-137 genes was only found in the epithelium but not in the connective tissue from patients with OLP. This raises the possibility to use miR-137 methylation as a biomarker for malignant prediction in patients with OLP.
Assuntos
Carcinoma de Células Escamosas/genética , Líquen Plano Bucal/genética , MicroRNAs/genética , Neoplasias Bucais/genética , Regiões Promotoras Genéticas/genética , Adulto , Fatores Etários , Consumo de Bebidas Alcoólicas , Biomarcadores Tumorais/análise , Transformação Celular Neoplásica/genética , Tecido Conjuntivo/patologia , Inibidor p16 de Quinase Dependente de Ciclina/análise , Epitélio/patologia , Feminino , Genes p16 , Humanos , Líquen Plano Bucal/patologia , Masculino , Metilação , MicroRNAs/análise , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Lesões Pré-Cancerosas/genética , Fatores de Risco , Fatores Sexuais , Fatores de TempoRESUMO
Recent profile studies of microRNA (miRNA) expression have documented a deregulation of miRNA (miR-320a) in human colorectal carcinoma. However, its expression pattern and underlying mechanisms in the development and progression of colorectal carcinoma has not been elucidated clearly. Here, we performed real-time PCR to examine the expression levels of miR-320a in colon cancer cell lines and tumor tissues. And then, we investigated its biological functions in colon cancer cells by a gain of functional strategy. Further more, by the combinational approaches of bioinformatics and experimental validation, we confirmed target associations of miR-320a in colorectal carcinoma. Our results showed that miR-320a was frequently downregulated in cancer cell lines and colon cancer tissues. And we demonstrated that miR-320a restoration inhibited colon cancer cell proliferation and ß-catenin, a functionally oncogenic molecule was a direct target gene of miR-320a. Finally, the data of real-time PCR showed the reciprocal relationship between miR-320a and ß-catenin's downstream genes in colon cancer tissues. These findings indicate that miR-320a suppresses the growth of colon cancer cells by directly targeting ß-catenin, suggesting its application in prognosis prediction and cancer treatment.
