例如:"lncRNA", "apoptosis", "WRKY"

The regulatory role of microRNA-1187 in TNF-α-mediated hepatocyte apoptosis in acute liver failure.

Int. J. Mol. Med.2012 Apr;29(4):663-8. doi:10.3892/ijmm.2012.888. Epub 2012 Jan 17
Dong Shan Yu 1 , Fang Mei An , Bang Dong Gong , Xiao Gang Xiang , Lan Yi Lin , Hui Wang , Qing Xie
Dong Shan Yu 1 , Fang Mei An , Bang Dong Gong , Xiao Gang Xiang , Lan Yi Lin , Hui Wang , Qing Xie
+ et al

[No authors listed]

Author information
  • 1 Department of Infectious Disease, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
全文

摘要


In the current study, we aimed at elucidating the regulatory mechanisms through which microR-1187 (miR-1187) participates in hepatocyte apoptosis in acute liver failure (ALF). An ALF model was induced with D-galactosamine (D-GalN) plus lipopolysaccharide (LPS) in BALB/c mice. The hepatic miRNA expression profile was detected by microarray analysis and verified by quantitative real-time PCR (qRT-PCR). The possible underlying mechanism was investigated in vitro using an embryonic murine hepatocyte cell line (BNLCL2) and miR-1187 mimic. Caspase-8 protein was detected by Western blotting and cell apoptosis was assayed by flow cytometry. Hepatic miR-1187 was down-regulated in ALF mice based on microarray data (P<0.001) and verified by qRT-PCR (P<0.01). Target scan revealed that caspase-8 was the putative target of miR-1187. In an in vitro study, miR-1187 showed the highest up-regulation in BNLCL2 cells transfected with the miR-1187 mimic at a 50 nM concentration for 12 h compared with cells transfected with the non-specific mimic (P<0.001). miR-1187 was down-regulated (P<0.01) but caspase-8 mRNA (P<0.01) as well as protein (P<0.05) were up-regulated in the BNLCL2 cells treated with D-GalN/TNF. Furthermore, overexpressed miR-1187 reduced caspase-8 expression at both the mRNA and protein levels significantly (P<0.01 and P<0.05 respectively), and significantly attenuated the apoptotic rate of BNLCL2 cells (P<0.05). We show that miR-1187 regulates hepatocyte apoptosis by targeting caspase-8. miR-1187 may serve as a potential therapeutic target for the treatment of ALF.