College of Pharmacy, Wonkwang University, Iksan 570-749, Republic of Korea.
Biochem Biophys Res Commun. 2013 Feb 15;431(3):572-8. doi: 10.1016/j.bbrc.2013.01.012. Epub 2013 Jan 11.
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.
硫磺黄素（3'，4'，6'-三羟基苯骈二氢吡喃酮）是从漆树中分离得到的一种重要黄酮类化合物，已知其具有抗炎和抗氧化应激作用。然而，硫磺黄素的抗癌特性及其作用机制仍知之甚少。在这里，我们表明在硫磺黄素刺激的细胞中，miR-30C 的表达明显增强，从而促进人癌细胞系的凋亡和细胞周期停滞。瞬时转染 pre-miR-30C 可使 PC-3 细胞的生长抑制率超过 70%，有力地证明了 miR-30C 选择性地抑制 cyclin D1 和 D2 的表达，但不抑制 cyclin D3。靶标验证分析表明 cyclin D2 的 3'-UTR 是 miR-30C 的直接靶标，而 miR-30C 对 cyclin D1 的抑制可能通过间接的 mRNA 调控发生。此外，沉默 miR-30C 的表达部分逆转了硫磺黄素诱导的细胞死亡。总之，我们的数据表明，肿瘤抑制 miRNA miR-30C 通过负调控 cyclin D1 和 D2 ，为硫磺黄素的抗癌特性做出贡献，为硫磺黄素和 miR-30C 用于人类癌症的治疗干预提供了重要意义。
