MODULATION OF E-CADHERIN AND HISTONE DEACETYLASE VIA MIR-34C TRANSFECTION IN EPIDERMOID CARCINOMA AND TONGUE CANCER

Background: Oral cancer is a multifactorial disease related to risk factors such as smoking, alcohol consumption, infection, and genetic liability, leading to epigenetic changes in oral epithelial cells with dysregulation of the cell cycle and abnormal proliferation of malignant cells, resulting in the formation of a tumor mass that does not respond to normal inhibitory signals. It is the most common type of head and neck cancer, accounting for approximately 90% of all head and neck cancers. MiR-34c is reported to be a member of the p53 pathway that may disrupt the cell cycle as a result of DNA damage. Thus, understanding the role of this miRNA in OSCC progression of OSCC becomes essential. Objective: To investigate whether miR-34c transfection in oral squamous carcinoma (SCC-25) and epidermoid carcinoma (A-253) cells alters their malignant behavior. Materials and Methods: The present study investigated the expression profile of miR-34c in patients with well-differentiated OSCC compared with tongue squamous cell carcinoma (SCC25) and human epidermoid carcinoma (A253) cells. A total of 25 tissue samples (10 normal oral mucosal tissue and 15 well-differentiated OSCC samples) were analyzed for miR-34c expression by qPCR. SCC25 and A253 cells were transfected with miR34c-5p expressing plasmid. After transfection, cells were tested for DNA content, apoptosis, and E-cadherin expression. Results: The expression of miR-34c was significantly lower in patients with well-differentiated OSCC than in normal oral mucosal tissues (p<0.001). Transfection of SCC25 and A253 cells with miR-34c induced cell cycle arrest and resulted in a significant increase in apoptosis (p<0.001). Additionally, E-cadherin expression was enhanced in OSCC compared to that in the control, with a significant decrease in the expression of all tested HDACs. Ultrasound-enhanced transfection of miR-34c-5p significantly forced cell cycle arrest and increased apoptosis levels, indicating the role of miR-34c-5p in controlling the malignant behavior of OSCC. Conclusion: miR-34c could be an important tumor suppressor in oral malignancy, and miRNA34c mimics may be a reliable approach to combat OSCC. Clinical relevance: Understanding the molecular functions of different types of miRNAs provides a deeper insight into understanding, and hence, combating, cancers such as OSCC. This may help minimize the need for invasive interventional treatments.