Up-Regulated Expression of miR-23a/b Targeted the Pro-Apoptotic Fas in Radiation-Induced thymic Lymphoma
| Autor: | Cong Liu, Fu Gao, Jianming Cai, Mingjuan Sun, Yanyong Yang, Wen Liu, Hu Liu, Ying Cheng, Bailong Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Untranslated region
Radiation induced thymic lymphoma Lymphoma Physiology miR-23 Down-Regulation Apoptosis Biology medicine.disease_cause lcsh:Physiology lcsh:Biochemistry Mice Cell Line Tumor Radiation Ionizing microRNA medicine Animals lcsh:QD415-436 fas Receptor 3' Untranslated Regions Thymic Lymphoma Cell Proliferation Regulation of gene expression Mice Inbred BALB C Binding Sites Base Sequence lcsh:QP1-981 Three prime untranslated region Thymus Neoplasms Oligonucleotides Antisense Fas Molecular biology BCL10 Up-Regulation MicroRNAs Radiation carcinogenesis NIH 3T3 Cells Carcinogenesis Sequence Alignment |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 32, Iss 6, Pp 1729-1740 (2013) |
| ISSN: | 1421-9778 1015-8987 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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