PRECLINICAL REPORTSmiR-155-5p antagonizes the apoptotic effect of bufalin in triple-negative breast cancer cellsWang, Qiana; Li, Cea; Zhu, Zhituc; Teng, Yueea; Che, Xiaofanga; Wang, Yana; Ma, Yanjua; Wang, Yidingb; Zheng, Huachuand; Liu, Yunpenga; Qu, XiujuanaAuthor Information aDepartment of Medical Oncology, The First Hospital of China Medical University bDepartment of Urology, The Liaoning Provincial Tumor Hospital, Shenyang cDepartment of Medical Oncology dCancer Research Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning, People’s Republic of China Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.anti-cancerdrugs.com). Correspondence to Xiujuan Qu, PhD, Department of Medical Oncology, The First Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang 110001, Liaoning, China Tel: +86 24 8328 2312; fax: +86 24 8328 2240; e-mail: [email protected] Received February 9, 2015 Accepted August 16, 2015 Anti-Cancer Drugs: January 2016 - Volume 27 - Issue 1 - p 9-16 doi: 10.1097/CAD.0000000000000296 Buy SDC Metrics Abstract Bufalin, a cardiotonic steroid isolated from toad venom, has been shown to kill various types of tumor cells. Our previous study showed that triple-negative breast cancer (TNBC) cells were less sensitive to bufalin than other types of breast cancer cells, but the reason for this lower sensitivity remains unclear. In this study, we showed that bufalin induced apoptosis in MDA-MB-231 and MCF-7/ADR TNBC cell lines, accompanied by increased miR-155-5p expression. Overexpression of miR-155-5p promoted proliferation and reduced bufalin-induced apoptosis of TNBC cells. In contrast, downregulation of miR-155-5p increased sensitivity to bufalin and upregulated the expression of FOXO3A. Bufalin also downregulated DNA methyltransferases 1 and 3a (DNMT1 and DNMT3a), and concurrent inhibition of DNMT1 and DNMT3a significantly increased miR-155-5p expression. These results indicate that miR-155-5p antagonizes bufalin sensitivity in TNBC cells, and that downregulation of DNMT1 and DNMT3a may be responsible for the bufalin-induced upregulation of miR-155-5p. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.