MicroRNA-376c Inhibits Cell Proliferation and Invasion in Osteosarcoma by Targeting to Transforming Growth Factor-Alpha

MicroRNAs are a class of small noncoding RNAs that function as critical gene regulators through targeting mRNAs for translational repression or degradation. In this study, we showed that miR-376c expression level was decreased while transforming growth factor-alpha (TGFA) mRNA expression levels were increased in osteosarcoma tissues and cell lines, and we identified TGFA as a novel direct target of miR-376c. Overexpression of miR-376c suppressed TGFA expression and the expression of its downstream signaling molecule such as epidermal growth factor receptor, and attenuated cell proliferation and invasion. Forced expression of TGFA could partly rescue the inhibitory effect of miR-376c in the cells. Taken together, these findings will shed light on the role and mechanism of miR-376c in regulating osteosarcoma cell growth via miR-376c/TGFA axis, and miR-376c may serve as a potential therapeutic target in osteosarcoma in the future. In osteosarcomas, there was an inverse relationship between the expression levels of miRNA-376c and TGFA. Experimental overexpression of miRNA-376c resulted in diminished quantities of TGFA mRNA and downstream molecules, including EGFR, attenuated cell proliferation, and tumor invasion. These data suggest that miRNA-376c might be a therapeutic target.