title: Up-regulated expression of miR-23a/b targeted the pro-apoptotic Fas in radiation-induced thymic lymphoma.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are small, single-stranded, noncoding RNAs, which usually bind to the 3'-untranslated region of target mRNAs and are capable of inducing posttranscriptional gene regulation by blocking translation or by degrading the target mRNA. However, the expression level of miR-23 in radiation induced carcinogenesis is largely unknown.
  
  
  METHODS
  Radiation induced thymic lymphoma model in BALB/c mice was set up. miR-23a & miR-23b miRNA levels in different tissues and cells were detected by real-time qPCR. miR-23a/b inhibitor and miR-23a/b mimics were transfected to lymphoma cells and the target of miR-23a/b was identified by microRNA target prediction and Luciferase assays.
  
  
  RESULTS
  We found that miR-23a & miR-23b were up-regulated in radiation induced thymic lymphoma tissue samples. Cell death and apoptosis were increased by miR-23a/b inhibitor and decreased by miR-23a/b mimics in lymphoma cells. Computational analysis found a putative target site of miR-23a/b in the 3'UTR of Fas mRNA, which was verified by luciferase reporter assay. Forced over-expression of miR-23a/b decreased the level of Fas protein. Moreover, over-expression of Fas rescued the pro-proliferation effect of miR-23, indicating Fas is a direct mediator of miR-23 functions. Furthermore, contrast to miR-23a/b which was up regulated, the Fas expression level was down-regulated and inversely correlated with miR-23 in split radiation induced lymphoma tissue samples. Finally, our data also indicates that miR-23a could repress Fas much more potent than miR-23b and the additional region besides conserved seed pairing enables miR-23a's higher regulation.
  
  
  CONCLUSIONS
  In this study, using a radiation induced thymic lymphoma model in BALB/c mice, We conclude that the expression of miR-23a/b is up-regulated in radiation-induced thymic lymphoma and it maybe a novel therapeutic target of that cancer.
authors.affiliation: Department of Radiation Medicine, Second Military Medical University, Shanghai, PR China.
authors.forename: Bailong
authors.initials: B
authors.lastname: Li
authors.forename: Mingjuan
authors.initials: M
authors.lastname: Sun
authors.forename: Fu
authors.initials: F
authors.lastname: Gao
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.forename: Yanyong
authors.initials: Y
authors.lastname: Yang
authors.forename: Hu
authors.initials: H
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.forename: Cong
authors.initials: C
authors.lastname: Liu
authors.forename: Jianming
authors.initials: J
authors.lastname: Cai
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation / Q000528:radiation effects; D008223:Lymphoma / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D041681:NIH 3T3 Cells; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D011839:Radiation, Ionizing; D016415:Sequence Alignment; D013953:Thymus Neoplasms / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000528:radiation effects; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C491899:Fas protein, mouse; D035683:MicroRNAs; C534062:Mirn23b microRNA, mouse; D016376:Oligonucleotides, Antisense; D019014:fas Receptor