Low expression of miR-let-7a promotes cell growth and invasion through the regulation of c-Myc in oral squamous cell carcinoma
Chunyang Luo, Jiyong Zhang, Yi Zhang, Xiao Zhang, Yinan Chen, Weimin Fan
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.