Norcantharidin modulates miR-655-regulated SENP6 protein translation to suppresses invasion of glioblastoma cells.

Norcantharidin (NCTD) is currently used as an anticancer drug for the treatment of some malignant cancers. However, whether it may have therapeutic effects on glioblastoma multiforme (GBM) remains unknown. Moreover, the underlying mechanisms have not been completely elucidated. Recently, SUMO-specific protease 6 (SENP6) has been shown as a tumor suppressor in some cancers. Nevertheless, whether it is involved in the pathogenesis of GBM has not been examined. Here, we studied the effects of NCTD on GBM cells. We found that NCTD dose-dependently increased SENP6 protein, but not messenger RNA (mRNA), in GBM cells, resulting in the suppression of cell invasion. Depletion of SENP6 in GBM cells significantly attenuated the NCTD-induced suppression of GBM cell invasion, while overexpression of SENP6 in GBM cells mimicked the effects of NCTD on cell invasion. Moreover, NCTD dose-dependently decreased the levels of microRNA-655 (miR-655), which bound to 3'-UTR of SENP6 mRNA to inhibit its translation. Overexpression of miR-655 decreased SENP6 in GBM cells, while depletion of miR-655 increased SENP6 protein in GBM cells. Taken together, our data demonstrates a previously unappreciated control of NCTD to suppress GBM cell invasion through modulation of miR-655-regulated SENP6 protein translation.