ABSTRACT
miR-758-3p plays an important role via regulting ABCA1-mediated cholesterol efflux in atherosclerosis. However, the mechanism of miR-758-5p in cholesterol metabolism is still unclear. Here, we revealed that miR-758-5p decreased total cholesterol accumulation in THP-1 macrophage derived foam cells through markedly reducing cholesterol uptake, and no effect on the cholesterol efflux. Interestingly, computational analysis suggests that CD36 may be a target gene of miR-758-5p. Our study further demonstrated that miR-758-5p decreased CD36 expression at both protein and mRNA levels via targeting the CD36 3'UTR in THP-1 macrophage derived foam cells. The present present study concluded that miR-758-5p decreases lipid accumulation of foam cell via regulating CD36-mediated the cholesterol uptake. Therefore, targeting miR-758-5p may offer a promising strategy to treat atherosclerotic vascular disease.
Subject(s)
3' Untranslated Regions , CD36 Antigens/genetics , Cholesterol/metabolism , Foam Cells/metabolism , MicroRNAs/genetics , RNA Isoforms/genetics , Base Sequence , Binding Sites , Biological Transport , CD36 Antigens/metabolism , Cell Line , Foam Cells/cytology , Gene Expression Regulation , Humans , MicroRNAs/metabolism , RNA Isoforms/metabolism , Signal TransductionABSTRACT
OBJECTIVE: To investigate the reversal effect of dihydromyricetin(DMY) on drug resistance of K562/A02 cells to adriamycin and explore its possible mechanism. METHODS: K562 and K562/A02 cells were treated with DMY (5, 10, 20, 40, 60, 80 and 100 mg/L) and ADM (100-0.05 mg/L) for 48 h. The viability of K562 cells and K562/A02 cells was tested and the reversal effect of DMY on drug resistance of K562/A02 cells to adriamycin was analyzed by MTT. The relative concentration of ADM in cells was measured by flow cytometry. Protein expressions of drug resistance related genes including P-glycoprotein (P-gp), multidrug resistance associated protein 1 (MRP1), glutathione transferase π (GSTπ) and BCL-2 were measured by Western Blot. RESULTS: The proliferation of K562 and K562/A02 cells was significantly decreased by DMY in dose-dependent manner as compared with control group (r1=0.37, r2=0.38). The IC50 of ADM on K562 and K562/A02 cells were 71.23±6.51 and 72.88±5.49 mg/L respectively. DMY (5, 10 and 20 mg/L) was low cytotoxicity. DMY (5, 10 and 20 mg/L) enhanced the sensitivity of K562/A02 cells to ADM in dose-dependent manner (r1=-0.62, r2=-0.71) and the reversal multiples was from 1.38 to 28.591. The relative concentrations of ADM in K562/A02 of DMY (5, 10 and 20 mg/L) group cells were significantly increased in dose-dependent manner compared with the control group (r=0.34). Compared with the control group, the expressions of drug resistance related protein P-gp, MRP1, GSTπ and BCL-2 were significantly decreased in dose-dependent manner in DMY (5, 10 and 20 mg/L) group (r1=-0.41, r2=-0.37, r3=-0.58, r=-0.46). Compared with the ADM group, the protein expressions of drug resistance related genes P-gp, MRP1, GSTπ and BCL-2 in DMY (5, 10 and 20 mg/L)+ADM group were significantly decreased in dose-dependent manner (r1=-0.55, r2=-0.41, r3 =-0.38, r4=-0.44). CONCLUSION: DMY enhances the sensitivity of K562/A02 cells to ADM, its mechanism may be related with decrease of P-gp, MRP1, GSTπ and BCL-2 expressions.
