环境化学致癌物反式苯丙芘可诱导人正常支气管上皮细胞恶性转化而癌变,这种恶性转化能否被遏制或逆转是一个关键，这也是研究癌症早期防治的突破点。临床前期试验发现三氧化二砷(ATO)治疗肺癌有良好的效果，但其临床应用不成熟,其抗恶性转化或癌变的机制仍不清楚。我们预实验发现ATO可抑制反式苯并芘恶性转化的人支气管上皮细胞的生长，而且这个过程中伴随有下调表达的癌基因miR-106b和MCM7。有研究报道miR-106b和MCM7是相互直接调控。生物信息学分析已显示miR-106b靶点LKB1及其下游p21等可间接调控MCM7。我们猜想ATO抗反式苯并芘恶性转化可能与抑制miR-106b-LKB1-MCM7信号通路有关。因此,本项目以分子克隆、稳定细胞株构建、报告基因系统等方法从正反两层次研究ATO抗恶性转化中miR-106b-MCM7通路的机制，这将加强ATO的临床潜力,也为肺癌早期防治指出了新方向。

Anti-benzo[a]pyrene-trans-7,8-diol-9,10-epoxide (anti-BPDE), an environmental chemical carcinogen, induced human bronchial epithelial cell into malignantly transformed or cancerated one. It's critical whether the malignant transformation is suppressed or not, which is a breakthrough point for the early prevention and therapy of cancer. The patients with various lung cancer benefits from the arsenic trioxide(ATO) treatment, but the clinical use of ATO and its anticarcinogenic mechanisms are undeveloped. The growth of anti-BPDE malignantly transformed human bronchial epithelial cell (16HBE-T) was inhibited by ATO, meanwhile the expression levels of oncogenes miR-106b and MCM7 were down-regul ated as shown in our preliminary experiments. The direct interaction of miR-106b and MCM7 was reported by researchers. Our bioinformatic analysis also showed that the target LKB1 for miR-106b and its down-stream protein p21 might indirectly modulate the MCM7. Therefore, the malignant transformation might be suppressed by ATO via the miR-106b-LKB1-MCM7 pathway. So, The molecular cloning, constructed stable cell and reporter gene system were used to study miR-106b-MCM7 pathway in anticarcinogenic mechanisms of ATO, which would help better understand its anticarcinogenic mechanisms, enhance its clinical potential and afford a new way for the early prevention and therapy of lung cancer.