title: Arsenic trioxide inhibits breast cancer cell growth via microRNA-328/hERG pathway in MCF-7 cells.
abstract: Arsenic trioxide (As2O3) has been widely used in the treatment of acute promyelocytic leukemia and has been observed to exhibit therapeutic effects in various types of solid tumor. In a previous study by this group, it was shown that As2O3 induces the apoptosis of MCF-7 breast cancer cells through inhibition of the human ether-à-go-go-related gene (hERG) channel. The present study was designed to further investigate the effect of As2O3 on breast cancer cells and to examine the mechanism underlying the regulation of hERG expression. The present study confirmed that As2O3 inhibited tumor growth in vivo, following MCF-7 cell implantation into nude mice. Using computational prediction , it was identified that microRNA (miR)-328 had a binding site in the 3'-untranslated region of hERG mRNA. A luciferase activity assay demonstrated that hERG is a target gene of miR-328. Further investigation using western blot analysis and reverse transcription-quantitative polymerase chain reaction revealed that As2O3 downregulated hERG expression via upregulation of miR-328 expression in MCF-7 cells. In conclusion, As2O3 was observed to inhibit breast cancer cell growth, at least in part, through the miR-328/hERG pathway.
authors.affiliation: Medical Functional Laboratory, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China.
authors.forename: Leqiu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China.
authors.forename: Changhao
authors.initials: C
authors.lastname: Yin
authors.affiliation: Department of Anatomy, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China.
authors.forename: Baizhu
authors.initials: B
authors.lastname: An
authors.affiliation: Medical Functional Laboratory, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China.
authors.forename: Yankun
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Medical Functional Laboratory, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wei
authors.affiliation: Medical Functional Laboratory, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Medical Functional Laboratory, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China.
authors.forename: Gaochen
authors.initials: G
authors.lastname: Song
mesh_terms: D020413:3' Untranslated Regions; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001665:Binding Sites; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology*; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D001152:Arsenicals; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C548170:MIRN328 microRNA, human; D035683:MicroRNAs; D010087:Oxides; D008156:Luciferases; D000077237:Arsenic Trioxide