Page 14 - D. Cancer biology
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[D. Cancer biology-11]



                  DDX3 expression by Serotonin receptor 7 through p53




                                                       Junho Lee¹

                             ¹Biotechnology, Chonnam National University, Gwangju 61186, Korea





        DDX3 is a host viral factor that can inhibit the hepatitis B virus induced innate immune responses. In this study, the
        20 bioactive compounds were screened the effects on DDX3 and we found that 5-HT upregulated DDX3 promoter
        activity via the 5-HT7 receptor on liver hepatocellular cells (HepG2 cells) by using a luciferase assay, RT-PCR analysis,

        and western blot analysis.    Furthermore, we are trying to elucidate the pathways involved in the stimulating effect

        of 5-HT on DDX3 expression to induce innate immune responses against hepatitis B virus infection. A knockdown
        of the 5-HT7 receptor by transfection si-5-HT7 receptors or si-control into HepG2 cells treated by 5-HT (or 5-HT
        plus agonist) confirmed the role of the 5-HT7 receptor in DDX3 expression. The IFN-β-Luc expression and level of

        hepatitis B virus surface Antigen (HBsAg) showed that DDX3 mediated by the 5-HT7 agonist (AS-19) increased IFN-
        β expression and inhibited HBV replication. Luciferase assays showed the involvement of 5-HT7 receptors in DDX3

        expression via cAMP/AC/PKA pathways by using protein kinas A (PKA) and adenylyl cyclase inhibitor (MDL 12330A).
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