Expression of miR-34a/p53 and their apoptotic target bax in oral squamous cell carcinoma

Abstract

Background and Objective: Identification of molecular targets for oral cancer is essential for developing therapeutic approaches that target those molecules. The miR-34a is a tumor suppressor gene and a transcriptional target of p53 protein. Bax is a pro-apoptotic protein which is activated by p53 and a target of miR-34a. The present study was designed to evaluate the expression levels of p53 and its transcriptional target miR-34a in oral squamous cell carcinoma cell line and to correlate this expression with their apoptotic target Bax. Materials and Methods: A total of 26 paraffin blocks were selected including 6 cases of normal oral mucosa, 10 cases of well differentiated oral squamous cell carcinoma and 10 cases of poorly differentiated oral squamous cell carcinoma. Sections from each block were subjected to quantitative real-time polymerase chain reaction analysis for quantification of miR-34a and p53 relative gene expression and immunohistochemical analysis was done to determine Bax protein expression. Results: The three studied proteins showed higher expression in normal oral mucosa than well differentiated oral squamous cell carcinoma and a lower expression in poorly differentiated oral squamous cell carcinoma. A statistically significant direct correlation was observed between the gene expression level of miR-34a and the expression level of Bax protein among studied cases and between the level of p53 gene expression and Bax protein expression. Conclusion: p53 dysfunction in oral carcinogenesis might lead to dysregulation of miR-34a and loss of apoptotic mechanism which gives the chance for the cancerous cells to proliferate and survive.