title: Dysregulation of the miR-34a-SIRT1 axis inhibits breast cancer stemness.
abstract: Enforced expression of miR-34a eliminates cancer stem cells in some malignant tumors. Sirtuin-1 (SIRT1) is a direct target of miR-34a. Here we found low levels of miR-34a and high levels of SIRT1 in CD44+/CD24- breast cancer stem cells (BCSCs). MiR-34a overexpression and knockdown of SIRT1 decreased proportion of BSCSs and mammosphere formation. Expression of CSC markers, ALDH1, BMI1 and Nanog was decreased. In nude mice xenografts, stable expression of miR-34a and silencing of SIRT1 reduced tumor burden. Taken together, our results demonstrated that miR-34a inhibits proliferative potential of BCSCs in vitro and in vivo, at least partially by downregulating SIRT1. The miR-34a-SIRT1 axis may play role in self-renewal of BCSCs.
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, China.|Department of Human Anatomy, Dalian Medical University, Dalian 116044, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ma
authors.affiliation: School of Pharmaceutical Sciences, Dalian University of Technology, Dalian 116024, China.|Genomics and Functional Proteomics Laboratories, Departments of Medicine and Medical Microbiology and Immunology, Creighton University Medical Center, NE 68131, USA.
authors.forename: Gary Guishan
authors.initials: GG
authors.lastname: Xiao
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, China.|The Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian 116044, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Mao
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Song
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian 116044, China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Fan
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, China.
authors.forename: Panhong
authors.initials: P
authors.lastname: Fan
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, China.
authors.forename: Zhenhuan
authors.initials: Z
authors.lastname: Hou
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, China.
authors.forename: Jiazhi
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, China.
authors.forename: Xiaotang
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian 116044, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, China.
authors.forename: Honghai
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Human Anatomy, Dalian Medical University, Dalian 116044, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Human Anatomy, Dalian Medical University, Dalian 116044, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, China.|The Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian 116044, China.
authors.forename: Lianhong
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D011897:Random Allocation; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: CD44+/CD24− BCSCs; SIRT1; miR-34α; stemness
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