破骨细胞和成骨细胞活动相关血清microRNA用于早期诊断前列腺癌骨转移及其分子机制的研究

前列腺癌是最易发生骨转移的恶性肿瘤之一。早期、准确诊断骨转移对临床分期及治疗有重要意义。最新研究表明，在骨转移早期，溶骨细胞活跃显著。我们前期研究中通过比较无骨转移、以成骨性骨转移为主、以溶骨性骨转移为主和无骨转移但有99mTc-MDP特异摄取的四类前列腺癌患者的血清miRNAs图谱，发现他们的miRNA表达有显著性差异。据此，我们将筛选出前列腺癌骨转移相关的血清miRNA，在前列腺癌患者中观察血清miRNA辅助诊断骨转移的价值，尤其溶骨性骨转移相关血清miRNA辅助早期预测和诊断骨转移的价值；并在体外实验中进一步确定溶骨和成骨活动相关miRNA作用的靶基因，以进一步阐明前列腺骨转移形成的相关分子机制。本项目将是国内外首次从血清miRNAs的层面揭示前列腺癌骨转移形成的过程中成骨和溶骨过程相关的miRNA分子调控机制，为未来肿瘤靶向治疗提供新的靶点。

Prostate cancer is the most commonly diagnosed cancer which is susceptible to bone metastases. Early and accurate diagnosis of bone metastases is important for clinical staging and treatment. Recent researches showed that osteoblastic differentiation and activation are essential parts of bone metastases. Our previous study found that the expression of miRNAs profile were significant difference in patients' serum between four different groups. We will screen and verify serum miRNA associated with bone metastasis of prostate cancer, and determine the target gene of miRNA in osteolytic and osteoblastic activity in vitro; then we will clarify the serum miRNA of molecular mechanism for bone metastasis of prostate cancer in our project. Meanwhile, we will observe the value of serum miRNA for diagnosis of bone metastases in patients with prostate cancer, especially for early prediction of bone metastasis associated with osteoblastic. This project will be the first study to explore the molecular mechanism of osteolytic and osteoblastic bone metastasis formation at the level of serum miRNAs, also provide a new avenue to targeted therapy for prostate cancer.