title: Can the microRNA expression profile help to identify novel targets for zoledronic acid in breast cancer?
abstract: Zoledronic acid (ZOL), belonging to third generation bisphosphonate family, is a potent inhibitor of osteoclast-mediated bone resorption, widely used to effectively prevent osteolysis in breast cancer patients who develop bone metastases. Low doses of ZOL have been shown to exhibit a direct anticancer role, by inhibiting cell adhesion, invasion, cytoskeleton remodelling and proliferation in MCF-7 breast cancer cells. In order to identify the molecular mechanisms and signaling pathways underlying the anticancer activity exerted by ZOL, we analyzed for the first time the microRNA expression profile in breast cancer cells. A large-scale microarray analysis of 377 miRNAs was performed on MCF7 cells treated with 10 μM ZOL for 24 h compared to untreated cells. Furthermore, the expression of specific ZOL-induced miRNAs was analyzed in MCF-7 and SkBr3 cells through Real-time PCR. Low-dose treatment with ZOL significantly altered expression of 54 miRNAs. Nine upregulated and twelve downregulated miRNAs have been identified after 24 h of treatment. Also, ZOL induced expression of 11 specific miRNAs and silenced expression of 22 miRNAs. MiRNA data analysis revealed the involvement of differentially expressed miRNAs in PI3K/Akt, MAPK, Wnt, TGF-β, Jak-STAT and mTOR signaling pathways, and regulation of actin cytoskeleton. Our results have been shown to be perfectly coherent with the recent findings reported in literature concerning changes in expression of some miRNAs involved in bone metastasis formation, progression, therapy resistance in breast cancer. In conclusion, this data supports the hypothesis that ZOL-induced modification of the miRNA expression profile contributes to the anticancer efficacy of this agent.
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Fanale
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Amodeo
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Bazan
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Insalaco
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Incorvaia
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Barraco
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Castiglia
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Rizzo
authors.affiliation: University Campus Bio-Medico, Department of Medical Oncology, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.affiliation: Fondazione Mediterranea "G.B. Morgagni", Catania, Italy.|Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Castorina
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics*; D004164:Diphosphonates / Q000494:pharmacology*; D020869:Gene Expression Profiling; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D061986:MCF-7 Cells; D059467:Transcriptome / Q000187:drug effects*; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
keywords: bone metastasis; breast cancer; miRNA expression profile; microarray analysis; zoledronic acid