Investigation of the role of Let-7a microRNA in inhibiting cell growth and proliferation and increasing drug sensitivity in oral cancer cells

Abstract

Oral cancer is a subset of head and neck cancers and one of the most common types of malignancy worldwide.Chemotherapy drugs, including Cisplatin, is one of the first and most effective treatments in the advanced stages of the disease.However, in addition to the harmful side effects, drug resistance in oral cancer cells limits the effect of chemotherapy and leads to the failure of successful treatment of patients.Let-7a is one of the most important microRNAs that play an important role in the differentiation and apoptosis of eukaryotic cells and is reduced in most human cancers.In this study, we try to investigate the effect of increasing the expression of this microRNA in inhibiting the growth of oral cancer cells and their sensitivity to chemotherapy. Cell viability, apoptosis, cell cycle distribution, cell migration ability and colony formation were analyzed using MTT, Annexin-V, flow cytometry, wound healing and colony formation methods, respectively. Changes in the expression of target genes were assessed using qRT-PCR. Increased expression of Let-7a in combination with Cisplatin significantly reduced cell proliferation, cell migration and colony formation of oral cancer cells. After combination therapy, HN-5 cells were stopped in phase G1 and G2 of the cell cycle. In addition, increased expression of Let-7a as a combination therapy with Cisplatin also increased cell apoptosis and increased the sensitivity of oral cancer cells to Cisplatin. This study shows that Let-7a plays an important role in carcinogenicity and sensitivity to chemotherapy drugs in oral cancer. Therefore, Let-7a is considered as a potential clinical biomarker and an important therapeutic target in oral cancer.