Low expression of miR-let-7a promotes cell growth and invasion through the regulation of c-Myc in oral squamous cell carcinoma

Abstract

In oral squamous cell carcinoma (OSCC), abnormal expression of microRNAs has been extensively reported. MiR-let-7a has been validated as a critical regulator of multiple cancers, but the biological process involved and its potential role in OSCC remain unknown.We first analyzed the differential expression of miR-let-7a in cancer tissues, adjacent noncancerous tissues and cell lines. The functional role of miR-let-7a in OSCC cell lines was evaluated by using colony formation assays, cell proliferation and transwell invasion assays in vitro. In addition, subcutaneous xenotransplantation of miR-let-7a transfected cells into nude mouse model was carried out to explore the potential function of miR-let-7a in vivo.miR-let-7a levels were found to be significantly downregulated in OSCC tissues compared with matched normal tissues (n = 60), and lower expression of miR-let-7a was related to poor prognosis in OSCC patients. Overexpression of MiR-let-7a induced a suppression in proliferation, invasion and migration and inhibited tumourigenesis in the nude mouse model. We also determined that c-Myc may serve as a direct target of miR-let-7a; furthermore, upregulated c-Myc expression could partially rescue the effects caused by miR-let-7a overexpression. miR-let-7a is low expression in OSCC, and promotes tumor development by directly targeting c-Myc. Our results may provide a potential therapeutic role for miR-let-7a in human OSCC.