title: microRNA-mediated survivin control of pluripotency.
abstract: Understanding the mechanisms that sustain pluripotency in human embryonic stem cells (hESCs) is an active area of research that may prove useful in regenerative medicine and will provide fundamental information relevant to development and cancer. hESCs and cancer cells share the unique ability to proliferate indefinitely and rapidly. Because the protein survivin is uniquely overexpressed in virtually all human cancers and in hESCs, we sought to investigate its role in supporting the distinctive capabilities of these cell types. Results presented here suggest that survivin contributes to the maintenance of pluripotency and that post-transcriptional control of survivin isoform expression is selectively regulated by microRNAs. miR-203 has been extensively studied in human tumors, but has not been characterized in hESCs. We show that miR-203 expression and activity is consistent with the expression and subcellular localization of survivin isoforms that in turn modulate expression of the Oct4 and Nanog transcription factors to sustain pluripotency. This study contributes to understanding of the complex regulatory mechanisms that govern whether hESCs proliferate or commit to lineages.
authors.affiliation: Stem Cell Technologies, Vancouver, BC, Canada.
authors.forename: Kristina
authors.initials: K
authors.lastname: Kapinas
authors.forename: Heesun
authors.initials: H
authors.lastname: Kim
authors.forename: Matthew
authors.initials: M
authors.lastname: Mandeville
authors.forename: Lori A
authors.initials: LA
authors.lastname: Martin-Buley
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
authors.forename: Jane B
authors.initials: JB
authors.lastname: Lian
authors.forename: Andre J
authors.initials: AJ
authors.lastname: van Wijnen
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stein
authors.forename: Dario C
authors.initials: DC
authors.lastname: Altieri
authors.forename: Gary S
authors.initials: GS
authors.lastname: Stein
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis; D039904:Pluripotent Stem Cells / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D034741:RNA, Small Interfering; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D018398:Homeodomain Proteins; D051034:Inhibitor of Apoptosis Proteins; C546703:MIRN203 microRNA, human; D035683:MicroRNAs; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D020033:Protein Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000077022:Survivin