RFX1 participates in doxorubicin-induced hepatitis B virus reactivation.
RFX1 participates in doxorubicin-induced hepatitis B virus reactivation.
复制标题
RFX1参与阿霉素诱导的乙型肝炎病毒再激活
作者：
Wang J;Jia J;Chen R;Ding S;Xu Q;Zhang T;Chen X;Liu S;Lu F
细胞毒性化疗药物，包括阿霉素，可以直接促进乙型肝炎病毒（HBV）复制，但其机制尚未完全阐明。本研究调查了细胞毒性化疗介导的直接促进 HBV 复制的潜在机制。我们发现阿霉素治疗同时促进了 HBV 复制和调节因子 X box 1 基因 (RFX1) 表达。在阿霉素治疗下，与 HBV 增强子 I 结合的 RFX1 量显着增加。此外，当内源性RFX1的表达被敲低，并且HBV增强子I的EP元件（介导RFX1和HBV增强子I结合的元件）发生突变时，阿霉素促进HBV复制的活性显着减弱。此外，在HBV基因型A-D中发现了两个不同的保守EP元件序列，阿霉素可以促进含有任一保守EP元件的HBV的复制。在这里，发现了阿霉素通过 RFX1 促进 HBV 复制的新途径，并且它可能参与阿霉素诱导的 HBV 再激活。这些发现将有助于预防抗癌化疗期间乙型肝炎病毒的再激活。
Cytotoxic chemotherapy drugs, including doxorubicin, can directly promote hepatitis B virus (HBV) replication, but the mechanism has not been fully clarified. This study investigated the potential mechanism underlying the cytotoxic chemotherapy‐mediated direct promotion of HBV replication. We found that HBV replication and regulatory factor X box 1 gene (RFX1) expression were simultaneously promoted by doxorubicin treatment. The amount of RFX1 bound to the HBV enhancer I was significantly increased under doxorubicin treatment. Furthermore, the activity of doxorubicin in promoting HBV replication was significantly attenuated when the expression of endogenous RFX1 was knocked down, and the EP element of HBV enhancer I, an element that mediated the binding of RFX1 and HBV enhancer I, was mutated. In addition, two different sequences of the conserved EP element were found among HBV genotypes A‐D, and doxorubicin could promote the replication of HBV harboring either of the conserved EP elements. Here, a novel pathway in which doxorubicin promoted HBV replication via RFX1 was identified, and it might participate in doxorubicin‐induced HBV reactivation. These findings would be helpful in preventing HBV reactivation during anticancer chemotherapy.
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