title: 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.
authors.affiliation: Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065, China.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Wang
authors.affiliation: Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zheng
authors.affiliation: Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065, China.|Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, 300457, China.
authors.forename: Tong-Cun
authors.initials: TC
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D026362:Serum Response Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D000903:Antibiotics, Antineoplastic; C431575:MRTFA protein, human; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C476858:SRF protein, human; D026362:Serum Response Factor; D015534:Trans-Activators; D004317:Doxorubicin
keywords: MRTF-A; Nrf2; drug resistance; hela