title: miR-155-5p antagonizes the apoptotic effect of bufalin in triple-negative breast cancer cells.
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.
authors.affiliation: 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.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Ce
authors.initials: C
authors.lastname: Li
authors.forename: Zhitu
authors.initials: Z
authors.lastname: Zhu
authors.forename: Yuee
authors.initials: Y
authors.lastname: Teng
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Che
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Yanju
authors.initials: Y
authors.lastname: Ma
authors.forename: Yiding
authors.initials: Y
authors.lastname: Wang
authors.forename: Huachuan
authors.initials: H
authors.lastname: Zheng
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Qu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002018:Bufanolides / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D002018:Bufanolides; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C022777:bufalin