Sulfuretin-induced miR-30C selectively downregulates cyclin D1 and D2 and triggers cell death in human cancer cell lines

Abstract

Sulfuretin (3',4',6'-trihydroxyaurone), one of the key flavonoids isolated from Rhus verniciflua, is known to suppress inflammation and oxidative stress. However, the anti-cancer properties of sulfuretin as well as its mechanism of action remain poorly understood. Here, we show that the expression of miR-30C is markedly enhanced in sulfuretin-stimulated cells, consequently promoting apoptosis and cell cycle arrest in human cancer cell lines. The transient transfection of pre-miR-30C resulted in greater than 70% growth inhibition in PC-3 cells and provided strong evidence that miR-30C selectively suppresses the expression of cyclin D1 and D2, but not cyclin D3. Target validation analysis revealed that 3'-UTR of cyclin D2 is a direct target of miR-30C, whereas suppression by miR-30C of cyclin D1 may occur through indirect mRNA regulation. In addition, silencing miR-30C expression partially reversed sulfuretin-induced cell death. Taken together, our data suggest that miR-30C, a tumor suppressor miRNA, contributes to anti-cancer properties of sulfuretin by negatively regulating cyclin D1 and D2, providing important implications of sulfuretin and miR-30C for the therapeutic intervention of human cancers.