摘要:
Rationale: Macrophage cholesterol homeostasis maintenance is the result of a balance between influx, endogenous synthesis, esterification/hydrolysis and efflux. Excessive accumulation of cholesterol leads to foam cell formation, which is the major pathology of atherosclerosis. Previous studies have shown that miR-27 (miR-27a and miR-27b) may play a key role in the progression of atherosclerosis. Objective: We set out to investigate the molecular mechanisms of miR-27a/b in intracellular cholesterol homeostasis. Methods and results: In the present study, our results have shown that the miR-27 family is highly conserved during evolution, present in mammals and directly targets the 3' UTR of ABCA1, LPL, and ACAT1. apoA1, ABCG1 and SR-B1 lacking miR-27 bind sites should not be influenced by miR-27 directly. miR-27a and miR-27b directly regulated the expression of endogenous ABCA1 in different cells. Treatment with miR-27a and miR-27b mimics reduced apoA1-mediated cholesterol efflux by 33.08% and 44.61% in THP-1 cells, respectively. miR-27a/b also regulated HDL-mediated cholesterol efflux in THP-1 macrophages and affected the expression of apoA1 in HepG2 cells. However, miR-27a/b had no effect on total cellular cholesterol accumulation, but regulated the levels of cellular free cholesterol and cholesterol ester. We further found that miR-27a/b regulated the expression of LPL and CD36, and then affected the ability of THP-1 macrophages to uptake Dil-oxLDL. Finally, we identified that miR-27a/b regulated cholesterol ester formation by targeting ACAT1 in THP-1 macrophages. Conclusion: These findings indicate that miR-27a/b affects the efflux, influx, esterification and hydrolysis of cellular cholesterol by regulating the expression of ABCA1, apoA1, LPL, CD36 and ACAT1. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
通讯机构:
[Xiao, Jianhua] U;Univ South China, Inst Pathogen Biol, Hengyang 421001, Hunan, Peoples R China.
摘要:
This article has been retracted: please see Elsevier Policy on Article Withdrawal.This article has been retracted at the request of the authors for the following reason: The results in Figure 4B are invalid because the conditions between the experimental group and the control group were not similar. The samples in the experimental group contained BSA whereas the samples in the control group did not. The authors found that BSA interferes with their experimental model and this makes the results invalid.
通讯机构:
[Xiao, Jianhua] U;Univ S China, Inst Pathogen Biol, Hengyang 421001, Hunan, Peoples R China.
关键词:
Schistosoma japonicum;eggshell protein gene;hammerhead ribozyme;in vitro cleavage;anti-reproduction
摘要:
Schistosoma japonicum (S. japonicum) is an extremely harmful pathogen, which infects humans and causes severe public health problems. To date, no effective therapeutic drugs for this pathogen are available. In this study, we designed and constructed three hammerhead ribozymes targeting the eggshell protein gene of S. japonicum (SjESG). The cleavage activities of these three ribozymes were determined using cleavage experiments. The in vitro cleavage results showed that among the three synthesized ribozymes (Rz1, Rz2 and Rz3), Rz1 and Rz3 cleaved their target RNAs effectively. However, Rz2 did not cleave its target RNA detectably. The putative therapeutic roles of these three ribozymes to inhibit the reproduction of S. japonicum in mice were studied in vivo. Compared with the negative controls, Rz1 and Rz3 treatments resulted in increased levels of IFN-γ but decreased levels of IL-4 in mice. Rz2 affected levels of IFN-γ and IL-4 to degrees similar with those caused by the vector controls. In addition, Rz1 and Rz3 reduced the amounts of adult worms and eggs in the livers of mice more extensively than Rz2 and the vector controls. Altogether, these results suggest a correlation between the in vitro cleavage abilities of Rz1 and Rz3 and their roles in reproduction inhibition of S. japonicum.
摘要:
Numerous microRNAs (miRNAs) play crucial roles in cancer development. In this study, we report that hsa-miR-96 is expressed at higher levels in human bladder urothelial carcinomas compared to normal tissues. We found that hsa-miR-96 increased invasion and differentiation of human bladder T24 cells and promoted their growth. Downregulation of hsa-miR-96 significantly affected the phenotype of bladder cancer T24 cells. The mRNA and protein levels of insulin receptor substrate 1 (IRS1) and MAP4K1 were significantly reduced in cells transfected with the hsa-miR-96 inhibitor when compared with levels in cells transfected with the empty plasmid vector or the negative control miRNA inhibitor. Altogether, these results suggest that hsa-miR-96 may affect the growth of bladder cancer cells by up-regulating IRS1 and MAP4K1 levels, functioning as a promising diagnostic marker in human bladder urothelial carcinomas.