Open AccessRFX 1 participates in doxorubicin‐induced hepatitis B virus reactivation
Author(s) -
Wang Jie,
Jia Junqiao,
Chen Ran,
Ding Shanlong,
Xu Qiang,
Zhang Ting,
Chen Xiangmei,
Liu Shuang,
Lu Fengmin
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1468
Subject(s) - doxorubicin , hepatitis b virus , virology , viral replication , cancer research , biology , enhancer , cytotoxic t cell , microbiology and biotechnology , chemistry , chemotherapy , gene expression , virus , gene , in vitro , biochemistry , genetics
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 ( RFX 1) expression were simultaneously promoted by doxorubicin treatment. The amount of RFX 1 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 RFX 1 was knocked down, and the EP element of HBV enhancer I, an element that mediated the binding of RFX 1 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 RFX 1 was identified, and it might participate in doxorubicin‐induced HBV reactivation. These findings would be helpful in preventing HBV reactivation during anticancer chemotherapy.