MiR-21 up-regulation mediates glioblastoma cancer stem cells apoptosis and proliferation by targeting FASLG.
To investigate whether miR-21 can affect the apoptosis and proliferation of glioblastoma cancer stem cells (GSCs) from down-regulating FASLG. The expression of miRNA-21 was detected by quantitative real-time PCR in normal brain tissue and glioblastoma samples, and the changes of miRNA-21 expression between GSCs and non-GSCs were also detected. The apoptosis and proliferation ability of miR-21 in GSCs were analyzed by MTT and flow cytometry assay after anti-miR-21 transfection. For the regulation mechanism analysis of miR-21, TargetScan, PicTar and microRNA were selected to predict some potential target genes of miR-21. The predicted gene was identified to be the direct and specific target gene of miR-21 by luciferase activities assay and western blot. RNA interference technology was used to confirm the apoptosis and proliferation effects of miR-21 were directly induced by FASLG. The expression of miR-21 increased significantly in glioblastoma contrast to normal brain tissue, and miR-21 up-regulated in GSCs remarkably. The proliferation of GSCs cell could be inhibited with high-expression of miR-21 and this effect could be restored by miR-21 knocked down. Mechanism analysis revealed that FASLG was a specific and direct target gene of miR-21. The advanced effects of anti-miR-21 on GSCs apoptosis and proliferation were mediated by expression of silenced FASLG. In summary, aberrantly expressed miR-21 regulates GSCs apoptosis and proliferation partly through directly down-regulating FASLG protein expression in GSCs and this might offer a new potential therapeutic stratagem for glioblastoma.
Department of Neurobiology, China Medical University, No. 92 Beier Road, Heping District, Shenyang, 110001, People's Republic of China.
Chao
C
Shang
Yan
Y
Guo
Yang
Y
Hong
Yun-hui
YH
Liu
Yi-xue
YX
Xue
D020413:3' Untranslated Regions; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D053222:Fas Ligand Protein / Q000737:chemistry / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D034622:RNA Interference; D015854:Up-Regulation
D020413:3' Untranslated Regions; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C524940:MIRN21 microRNA, human; D035683:MicroRNAs