慢性炎症在炎症性疾病向恶性肿瘤转化中扮演着十分重要的角色，但是促进肝脏炎癌转变的具体机制仍然不得而知。本研究以慢性肝炎、肝硬化向肝癌的转变为突破口，利用手术切除肝癌标本筛选出促进慢性肝炎转化为肝癌的重要因子Miz1。通过构建小鼠炎癌模型发现Miz1在进展为肝癌的过程中其表达是逐渐降低的，同时伴随着增殖和凋亡水平的增高。而促炎因子IL-1α、TNF-α、IL-6、MCP1的表达则是逐渐增多的。进一步的利用组织特异性敲除技术得到肝脏特异性Miz1基因全敲的小鼠Miz1(∆hep)及细胞核内POZ结构域特异性敲除的小鼠Miz1(∆POZ−hep)。拟通过上述基因敲除小鼠阐明Miz1通过细胞浆还是细胞核抑制肝脏非可控性炎症恶性转化的分子机制。本课题的开展将有助于发现干预和控制非可控性炎症恶性转化的新方法，从而为慢性肝炎、肝癌及其它慢性炎症性疾病的治疗打下理论基础。

Chronic inflammation plays a vital role in the transformation from inflammation to cancer. However, the underlying mechanism is still unknown. We select the common transformation in China from chronic hepatitis, cirrhosis to liver cancer as a model for carcinogenesis from non-resolving inflammation, using hepatocellular carcinoma (HCC) specimens from surgical resection and screening out the key factor Miz1 in the transformation from inflammation to cancer. By constructing the animal model, we found that Miz1 was significantly down-regulated in the oncogenesis and development of HCC, accompying by the increased proliferating and apoptosis. Whereases, pro-inflammatory cytokines, such as IL-1α、TNF-α、IL-6、MCP1, were significantly increased in the process. By using conditional knock out technic we have got liver-specific full-length Miz1 and Miz(∆POZ) knockout mice, further clarification of the mechanism underlying nuclear/cytoplasmic Miz1 in the transformation from inflammation to cancer. These researches are targeting for discovering novel methods in prevention and modulation of carcinogenesis from non-resolving inflammation, and establishing the theory basis for treatment of chronic hepatitis, liver cancer and other chronic diseases.