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.