Downregulations of B-cell lymphoma 2 and myeloid cell leukemia sequence 1 by microRNA 153 induce apoptosis in a glioblastoma cell line DBTRG-05MG.
MicroRNA-153 (miR-153) is a brain-specific miRNA that is expressed at a significantly lower level in glioblastoma (GBM) relative to non-neoplastic brain tissue. Although the expression pattern of miR-153 has been extensively established, its target genes and cellular mechanism remain undefined. To investigate into the potential function of miR-153 in glioblastmas, we transfected a GBM cell line DBTRG-05MG with synthetic miR-153 oligos and observed decreased cell proliferation and increased apoptosis. Bioinformatics analysis revealed that anti-apoptosis family member B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia sequence 1 (Mcl-1) are potential targets of miR-153. Indeed, Western blot analysis indicated that miR-153 downregulated both Bcl-2 and Mcl-1 at the protein levels. Single strand miR-153 inhibitor, which forms complementary base-pair with endogenous miR-153, efficiently blocked the apoptosis and target protein degradation induced by overexpression of miR-153. By luciferase reporter assays, we further showed that miR-153 inhibited Bcl-2 and Mcl-1 expressions by directly targeting the 3'UTR regions of their respective mRNAs.
Xu
Jianzhen
J
Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Liao
Xuemei
X
Wong
Chiwai
C
D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D016393:Lymphoma, B-Cell / Q000473:pathology*; D035683:MicroRNAs / Q000494:pharmacology* / Q000627:therapeutic use; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000235:genetics*; D014162:Transfection / Q000379:methods
D020413:3' Untranslated Regions; C579095:MCL1 protein, human; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2