title: miR-326 associates with biochemical markers of bone turnover in lung cancer bone metastasis.
abstract: Recent evidence suggests that miRNAs could be used as serum markers in a variety of normal and pathological conditions. In this study, we aimed to identify novel miRNAs associated with skeletal metastatic disease in a preclinical model of lung cancer bone metastasis. We assessed the validity of these miRNAs as reliable serum biochemical markers to monitor the extent of disease and response to treatment in comparison to imaging techniques and standard biochemical markers of bone turnover. Using a murine model of human lung cancer bone metastasis after zoledronic acid (ZA) treatment, PINP (procollagen I amino-terminal propeptide) was the only marker that exhibited a strong correlation with osteolytic lesions and tumor burden at early and late stages of bone colonization. In contrast, BGP (osteocalcin) and CTX (carboxyterminal telopeptide) demonstrated a strong correlation only at late stages. We performed qPCR based screening of a panel of 380 human miRNAs and quantified bone metastatic burden using micro-CT scans, X-rays and bioluminescence imaging. Interestingly, levels of miR-326 strongly associated with tumor burden and PINP in vehicle-treated animals, whereas no association was found in ZA-treated animals. Only miR-193 was associated with biochemical markers PINP, BGP and CTX in ZA-treated animals. Consistently, miR-326 and PINP demonstrated a strong correlation with tumor burden. Our findings, taken together, indicate that miR-326 could potentially serve as a novel biochemical marker for monitoring bone metastatic progression.
authors.affiliation: Adhesion and Metastasis Laboratory, Division of Oncology, Center for Applied Biomedical Research (CIMA), University of Navarra, Pamplona, Spain.
authors.forename: Karmele
authors.initials: K
authors.lastname: Valencia
authors.forename: Marta
authors.initials: M
authors.lastname: Martín-Fernández
authors.forename: Carolina
authors.initials: C
authors.lastname: Zandueta
authors.forename: Cristina
authors.initials: C
authors.lastname: Ormazábal
authors.forename: Susana
authors.initials: S
authors.lastname: Martínez-Canarias
authors.forename: Eva
authors.initials: E
authors.lastname: Bandrés
authors.forename: Concepción
authors.initials: C
authors.lastname: de la Piedra
authors.forename: Fernando
authors.initials: F
authors.lastname: Lecanda
mesh_terms: D015415:Biomarkers; D001859:Bone Neoplasms / Q000556:secondary*; D016723:Bone Remodeling; D045744:Cell Line, Tumor; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008958:Models, Molecular; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers