Explore the relationship of Epstein-Barr virus microRNA BART9 and TGFβ signaling in nasopharyngeal carcinoma
| Autor: | Mei Ling Lin, 林美齡 |
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| Rok vydání: | 2012 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 100 EBV encoded microRNA BART9 is highly expressed in nasopharyngeal carcinoma (NPC) tissue. However, its role in NPC pathogenesis is unclear. Computational prediction identified TGFβRII as potential target of BART9. This study investigated the role of BART9 in TGFβ-induced growth inhibition and the associated signaling pathways in NPC. Cultured NPC cells stably expressing LacZ control and BART9 were treated with 5 ng/mL of TGF-β1 for up to five days. Cell growth was determined using MTS assay and DAPI staining. The effects of BART9 on TGFβRII mRNA and protein levels were determined by qRT-PCR and Western blot respectively. The effects of BART9 on TGFβRII signaling components and down-stream targets were also quantified by qRT-PCR and Western blot. TGF-β1 at 5 ng/mL significantly suppressed proliferation of cultured NPC cells. Ectopic expression of BART9 completely inhibited the growth inhibitory effect of TGF-β1. Ectopic expression of BART9 in NPC cells suppressed the mRNA and protein levels of TGFβRII and inhibited SMAD2 phosphorylation and SMAD4 expression. The effect of BART9 on TGF β signaling components was reversed by the addition of LNA-modified anti-BART9 oligonucleotide. These results indicated that TGFβRII is a direct target of BART9 and suggested that BART9 may protect NPC cells from TGFβ-mediated growth inhibition by downregulating TGFβRII. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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