title: MicroRNAs and bone metastasis: a new challenge.
abstract: The development of bone metastases requires multistep and multicellular machinery consisting not only of processes shared with any type of metastases (formation of a pre-metastatic niche, chemotaxis of tumor cells into the host tissue, tumor cells escape from the microvasculature), but also biological interactions that are strictly related to the particular bone microenvironment (bone marrow colonization by cancer cells, osteomimicry, deregulation of bone homeostasis). MiRNAs are highly conserved, small RNAs molecules that regulate gene expression. The functional consequence of miRNA deregulation lies in the mRNA targets whose expression is altered. MiRNA networks acting as upstream regulators of these genes interfere with the initial steps of tumor local invasion and cancer cell intravasation, mainly by regulating the epithelial-mesenchymal transition, the motility, invasiveness and survival abilities of these cells. The miRNA-mediated regulation on the steps of bone tropism, anchorage, homing and finally bone colonization is more tissue specific, being dependent on the expression pattern of target miRNAs in bone marrow sinusoids, bone cells and microenvironment. In that, miRNA specific expression signatures that can distinguish between primary tumors from their corresponding bone metastases might be determinants of clinical aggressiveness. In this review, we focus on the current advances on functions and molecular mechanisms by which miRNAs exert their biological roles in regulating bone metastases development.
authors.affiliation: Institut national de la santé et de la recherche médicale (INSERM), UMR 1033, Lyon F-69008, France. martine.croset@inserm.fr.
authors.forename: Martine
authors.initials: M
authors.lastname: Croset
authors.affiliation: Medical Oncology, Campus Bio-Medico University of Rome, Rome 00128, Italy. d.santini@unicampus.it.
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.affiliation: Medical Oncology, Campus Bio-Medico University of Rome, Rome 00128, Italy. m.iuliani@unicampus.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Iuliani
authors.affiliation: Medical Oncology, Campus Bio-Medico University of Rome, Rome 00128, Italy. m.fioramonti@unicampus.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Fioramonti
authors.affiliation: Medical Oncology, Campus Bio-Medico University of Rome, Rome 00128, Italy. a.zoccoli@unicampus.it.
authors.forename: Alice
authors.initials: A
authors.lastname: Zoccoli
authors.affiliation: Medical Oncology, Campus Bio-Medico University of Rome, Rome 00128, Italy. b.vincenzi@unicampus.it.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.affiliation: Medical Oncology, Campus Bio-Medico University of Rome, Rome 00128, Italy. g.tonini@unicampus.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
authors.affiliation: Medical Oncology, Campus Bio-Medico University of Rome, Rome 00128, Italy. f.pantano@unicampus.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pantano
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009362:Neoplasm Metastasis; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D035683:MicroRNAs; D012334:RNA, Neoplasm