MRTF-A can activate Nrf2 to increase the resistance to doxorubicin

Abstract

Chemotherapeutic drugs resistance was considered to be the major obstacle for cancer therapy. MRTF-A, co-activators of serum response factor (SRF), promoted tumor cell invasion and metastasis in cancer. So far there has been no relevant reports about MRTF-A' role in tumor chemotherapy. Here, we reported that MRTF-A overexpression conferred resistance to doxorubicin mediated apoptosis by significantly increasing the expression of Nrf2 which was an important molecule associated with the resistance of anticancer drugs. If MRTF-A was knocked down, could the corresponding results be obtained? Moreover, we showed that overexpression MRTF-A had no remarkable effect to doxorubicin mediated apoptosis in cancer cells when knocking down Nrf2. Further studies showed that MRTF-A regulated the transcriptional activity of Nrf2 by forming a complex with SRF binding to the CarG box which existed on Nrf2 promoter region. On the whole, our study revealed a novel possible resistant pathway to doxorubicin.