A negative feedback loop of H19/miR‐675/VDR mediates therapeutic effect of cucurmin in the treatment of glioma

Abstract 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) 2 D 3 ) 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) 2 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.