Department of Neurosurgery, The First Hospital Affiliated to Army Medical University (Southwest Hospital), Chongqing, China.
J Cell Physiol. 2020 Mar;235(3):2171-2182. doi: 10.1002/jcp.29127. Epub 2019 Aug 29.
Curcumin (CUR) shows a remarkable antitumor activity against a wide range of cancers such as glioma, but its underlying mechanism remains elusive. In this study, we aimed to explore the potential role of H19/miR-675/vitamin D receptor (VDR) in the effect of CUR against glioma. Real-time polymerase chain reaction and western-blot analysis were used to study the effect of CUR or 1,25-dihydroxyvitamin D (1,25(OH) D ) on the expression of H19, miR-675, and VDR. In addition, the effect of H19 on VDR expression was also studied. Furthermore, the expression of H19, miR-675, and VDR between CUR-loaded nanoparticles (NPs) and NP groups was compared, and the interaction among H19, miR-675, and VDR was analyzed by in-silicon and luciferase assays. In a dose-dependent manner, CUR and 1,25(OH) D3 both downregulated the expression of H19 and miR-675 but increased the expression of VDR. In addition, H19 evidently reduced the mRNA and protein levels of VDR. Furthermore, VDR was confirmed as a target gene of miR-675, which significantly reduced the expression of VDR. Finally, the administration of CUR evidently decreased tumor volume. CUR-loaded NP group exhibited lower levels of H19 and miR-675, while the NP group showed higher levels of VDR mRNA and protein. In summary, it is the first time that the involvement of a negative feedback loop of H19/miR-675/VDR has been demonstrated in the development of glioma. Therefore, H19 might serve as a new biomarker for the diagnosis and treatment of glioma.
姜黄素（CUR）对多种癌症（如神经胶质瘤）具有显著的抗肿瘤活性，但作用机制尚不清楚。本研究旨在探讨 H19/miR-675/维生素 D 受体（VDR）在 CUR 抑制神经胶质瘤中的潜在作用。实时聚合酶链反应和 Western blot 分析用于研究 CUR 或 1,25-二羟基维生素 D（1,25（OH）D）对 H19、miR-675 和 VDR 表达的影响。此外，还研究了 H19 对 VDR 表达的影响。进一步比较 CUR 载药纳米粒（NPs）组和 NP 组之间 H19、miR-675 和 VDR 的表达，通过计算机模拟和荧光素酶报告基因检测分析 H19、miR-675 和 VDR 之间的相互作用。CUR 和 1,25（OH）D3 均呈剂量依赖性地下调 H19 和 miR-675 的表达，增加 VDR 的表达。此外，H19 明显降低了 VDR 的 mRNA 和蛋白水平。此外，VDR 被证实为 miR-675 的靶基因，显著降低了 VDR 的表达。最后，CUR 的给药明显降低了肿瘤体积。CUR 载药 NP 组 H19 和 miR-675 水平较低，NP 组 VDR mRNA 和蛋白水平较高。总之，这是首次证明 H19/miR-675/VDR 的负反馈环参与了神经胶质瘤的发生发展。因此，H19 可能成为神经胶质瘤诊断和治疗的新生物标志物。
