title: 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.
authors: College of Pharmacy, Wonkwang University, Iksan 570-749, Republic of Korea.
authors: Suman
authors: S
authors: Poudel
authors: Jinsoo
authors: J
authors: Song
authors: Eun-Jung
authors: EJ
authors: Jin
authors: Kyung
authors: K
authors: Song
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001572:Benzofurans / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000037:antagonists & inhibitors*; D056742:Cyclin D2 / Q000037:antagonists & inhibitors*; D015536:Down-Regulation; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D001572:Benzofurans; D056742:Cyclin D2; D005419:Flavonoids; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D019938:Cyclin D1; C054989:sulfuretin