title: MicroRNA miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survival.
abstract: Several microRNA (miRNA) loci are found within genomic regions frequently deleted in primary neuroblastoma, including miR-885-5p at 3p25.3. In this study, we demonstrate that miR-885-5p is downregulated on loss of 3p25.3 region in neuroblastoma. Experimentally enforced miR-885-5p expression in neuroblastoma cell lines inhibits proliferation triggering cell cycle arrest, senescence and/or apoptosis. miR-885-5p leads to the accumulation of p53 protein and activates the p53 pathway, resulting in upregulation of p53 targets. Enforced miR-885-5p expression consistently leads to downregulation of cyclin-dependent kinase (CDK2) and mini-chromosome maintenance protein (MCM5). Both genes are targeted by miR-885-5p via predicted binding sites within the 3'-untranslated regions (UTRs) of CDK2 and MCM5. Transcript profiling after miR-885-5p introduction in neuroblastoma cells reveals alterations in expression of multiple genes, including several p53 target genes and a number of factors involved in p53 pathway activity. Taken together, these data provide evidence that miR-885-5p has a tumor suppressive role in neuroblastoma interfering with cell cycle progression and cell survival.
authors.affiliation: Department of Tumor Genetics, B030, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg, Germany.
authors.forename: E A
authors.initials: EA
authors.lastname: Afanasyeva
authors.forename: P
authors.initials: P
authors.lastname: Mestdagh
authors.forename: C
authors.initials: C
authors.lastname: Kumps
authors.forename: J
authors.initials: J
authors.lastname: Vandesompele
authors.forename: V
authors.initials: V
authors.lastname: Ehemann
authors.forename: J
authors.initials: J
authors.lastname: Theissen
authors.forename: M
authors.initials: M
authors.lastname: Fischer
authors.forename: M
authors.initials: M
authors.lastname: Zapatka
authors.forename: B
authors.initials: B
authors.lastname: Brors
authors.forename: L
authors.initials: L
authors.lastname: Savelyeva
authors.forename: V
authors.initials: V
authors.lastname: Sagulenko
authors.forename: F
authors.initials: F
authors.lastname: Speleman
authors.forename: M
authors.initials: M
authors.lastname: Schwab
authors.forename: F
authors.initials: F
authors.lastname: Westermann
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D056426:Genetic Loci; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D017384:Sequence Deletion; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; C489423:MCM5 protein, human; D035683:MicroRNAs; D012334:RNA, Neoplasm; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2