1. In vivo NCL targeting affects breast cancer aggressiveness through miRNA regulation
- Author
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Pierluigi Gasparini, Dario Palmieri, Jessica Consiglio, Flavia Pichiorri, Gerard J. Nuovo, Claudia Piovan, Michael A. Freitas, Tiffany Talabere, Alessandro Laganà, Stefano Volinia, Carlo M. Croce, Vincenzo Coppola, Jia You, Guido Marcucci, Veronica Balatti, Alberto Rocci, Jingwen Guan, Luciana De Luca, Craig C. Hofmeister, Charles L. Shapiro, John C. Byrd, and Luciano Cascione
- Subjects
Transcription, Genetic ,Nude ,genetics/metabolism ,Drug resistance ,Bioinformatics ,Mice ,0302 clinical medicine ,Immunology and Allergy ,genetics ,Neoplasm Metastasis ,skin and connective tissue diseases ,Fulvestrant ,0303 health sciences ,Tumor ,Estradiol ,RNA-Binding Proteins ,food and beverages ,Aptamers, Nucleotide ,3. Good health ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Oligodeoxyribonucleotides ,030220 oncology & carcinogenesis ,Gene Knockdown Techniques ,Nucleotide ,pharmacology, Breast Neoplasms ,genetics/pathology, Cell Line ,Tumor, Cell Proliferation, Estradiol ,analogs /&/ derivatives/pharmacology, Female, Gene Expression Regulation ,Neoplastic, Gene Knockdown Techniques, Gene Silencing, Genes ,genetics, Guanine, HEK293 Cells, Humans, Mice, Mice ,Nude, MicroRNAs ,genetics/metabolism, Neoplasm Invasiveness, Neoplasm Metastasis, Oligodeoxyribonucleotides ,pharmacology, Phosphoproteins ,metabolism, RNA-Binding Proteins ,Female ,Guanine ,Aptamer ,Immunology ,Mice, Nude ,Breast Neoplasms ,Biology ,Article ,Cell Line ,03 medical and health sciences ,Breast cancer ,In vivo ,Cell Line, Tumor ,microRNA ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Gene Silencing ,Gene ,030304 developmental biology ,Cell Proliferation ,Neoplastic ,fungi ,genetics/pathology ,Cell Biology ,medicine.disease ,Phosphoproteins ,In vitro ,MicroRNAs ,HEK293 Cells ,Gene Expression Regulation ,Genes ,pharmacology ,analogs /&/ derivatives/pharmacology ,Nucleolin ,metabolism ,030215 immunology ,Genes, Neoplasm - Abstract
The regulatory protein nucleolin controls the expression of a subset of miRNAs involved in breast cancer progression and can be targeted to inhibit breast cancer growth in vivo., 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.
- Published
- 2013