Curcumin affects the prognosis of renal cell carcinoma (RCC) through a negative feedback loop of H19/miR-675/HDAC/CTCF

Abstract

IntroductionThe objective of this study was to explore the role of Curcumin (CUR) in the control of renal cell carcinoma (RCC) as well as the molecular mechanism underlying the effect of CUR.Material and methodsReal-time PCR, Western-blot analysis, immunohistochemistry (IHC) assay, and luciferase assay were utilized to detect the effect of CUR.ResultsMesoscale nanoparticles (particles) could be safely and preferentially accumulated in the kidney in a dose-dependent manner, and the specific localization of particles in the kidney reached its maximum level at a dose of 25 mg/kg. Treatment with CUR alleviated RCC by up-regulating the expression of H19 and miR-675 while down-regulating the expression of HDAC1 and HDAC6 in RCC rats. Furthermore, the underlying mechanism of CUR in the regulation of H19 was explored, and it was revealed that CUR increased H19 expression via increasing the translational efficiency of H19 promoter. Therefore, the treatment with CUR increased the levels of H19 and miR-675 mRNAs while reducing the expression of HDAC1 and HDAC6. According to a computational analysis, HDAC1 and HDAC6 were both direct targets downstream of miR-675, and miR-675 mimics could decrease the luciferase activity of cells transfected by wild-type HDAC1 and HDAC6 3’UTR. In addition, miR-675 but not CTCF reduced the protein levels of HDAC1 and HDAC6. Nevertheless, CTCF increased the luciferase activity of cells transfected by H19 promoter, while miR-675 mimics decreased the effect of CTCF.ConclusionsIn this study, we suggested that CUR could affect the prognosis of RCC by establishing a negative feedback loop of H19/miR-675/HDAC/CTCF.