| Summary: | 碩士 === 國立臺灣大學 === 微生物學研究所 === 97 === The major cause of cervical cancer is infection of human papillomavirus type 16 (HPV-16), which pathogenicity and oncogenicity are correlated with the hormone glucocorticoid. Previous studies have shown that glucocorticoid upregulates the transcription activity through the three glucocorticoid response elements (GREs) in HPV-16 long control region (LCR), enhancing the expression of the two major oncogenes E6 and E7 downstream, resulting in cell transformation and oncogenesis.
Moreover, GR belongs to Type I nuclear receptor family and serves as transcription factor. When treated with ligand, GR binds to the GREs upstream of its target genes and recruits other coregulators to exert its function, implicating that the cofactors of GR may play roles in the regulation of HPV-16. Previously, our lab found a novel cofactor of GR, named NRIP, which was demonstrated to upregulate the transactivity of GR. Hence, we investigate the roles of GR and its coactivator NRIP in the regulation of HPV-16. First, we demonstrated that GR bound to the GRE(s) in HPV-16 LCR upon ligand dexamethosome (Dex) treatment by chromatin immunoprecipitation (ChIP). The results of luciferase activity assays not only proved the three unknown GREs were separately functional, but also revealed the existence of the fourth GRE. We also proved that NRIP bound HPV-16 LCR through GR in the presence of Dex. Knockdown of NRIP downregulated the mRNA expression of HPV-16 E6 and E7, and also decreased the cell proliferation promoted by Dex.
These results indicate that GR enhances the transcription activity of HPV-16 LCR by binding to the four GREs, and cofactor NRIP also plays an important role in GR-mediated regulation.
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