title: In vivo NCL targeting affects breast cancer aggressiveness through miRNA regulation.
abstract: Numerous studies have described the altered expression and the causal role of microRNAs (miRNAs) in human cancer. However, to date, efforts to modulate miRNA levels for therapeutic purposes have been challenging to implement. Here we find that nucleolin (NCL), a major nucleolar protein, posttranscriptionally regulates the expression of a specific subset of miRNAs, including miR-21, miR-221, miR-222, and miR-103, that are causally involved in breast cancer initiation, progression, and drug resistance. We also show that NCL is commonly overexpressed in human breast tumors and that its expression correlates with that of NCL-dependent miRNAs. Finally, inhibition of NCL using guanosine-rich aptamers reduces the levels of NCL-dependent miRNAs and their target genes, thus reducing breast cancer cell aggressiveness both in vitro and in vivo. These findings illuminate a path to novel therapeutic approaches based on NCL-targeting aptamers for the modulation of miRNA expression in the treatment of breast cancer.
authors.affiliation: Division of Hematology, College of Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA. flavia.pichiorri@osumc.edu
authors.forename: Flavia
authors.initials: F
authors.lastname: Pichiorri
authors.forename: Dario
authors.initials: D
authors.lastname: Palmieri
authors.forename: Luciana
authors.initials: L
authors.lastname: De Luca
authors.forename: Jessica
authors.initials: J
authors.lastname: Consiglio
authors.forename: Jia
authors.initials: J
authors.lastname: You
authors.forename: Alberto
authors.initials: A
authors.lastname: Rocci
authors.forename: Tiffany
authors.initials: T
authors.lastname: Talabere
authors.forename: Claudia
authors.initials: C
authors.lastname: Piovan
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lagana
authors.forename: Luciano
authors.initials: L
authors.lastname: Cascione
authors.forename: Jingwen
authors.initials: J
authors.lastname: Guan
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Gasparini
authors.forename: Veronica
authors.initials: V
authors.lastname: Balatti
authors.forename: Gerard
authors.initials: G
authors.lastname: Nuovo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Coppola
authors.forename: Craig C
authors.initials: CC
authors.lastname: Hofmeister
authors.forename: Guido
authors.initials: G
authors.lastname: Marcucci
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.forename: Stefano
authors.initials: S
authors.lastname: Volinia
authors.forename: Charles L
authors.initials: CL
authors.lastname: Shapiro
authors.forename: Michael A
authors.initials: MA
authors.lastname: Freitas
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D052138:Genes, Neoplasm / Q000235:genetics; D006147:Guanine; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation; D000097796:Nucleolin
chemical_list: D052157:Aptamers, Nucleotide; D004958:Estradiol; D000077267:Fulvestrant; D006147:Guanine; D035683:MicroRNAs; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C513936:AGRO 100