微囊藻毒素-LR（MC-LR）是水体水华产生的有毒藻类毒素，流行病学研究表明肝癌的发生与MC-LR污染有关，但其致癌机制未明。申请者预实验发现MC-LR诱导永生化正常人肝细胞发生恶性转化时，长链非编码RNA（LncRNA）H19、HULC及HOTAIR表达上调，MEG3及AFAP1-AS1表达下调，推测LncRNA可能参与MC-LR的致癌效应。本课题拟通过肝细胞恶性转化模型，利用LncRNA芯片筛选并经qRT-PCR技术验证不同转化时期细胞中的差异表达LncRNA，确立影响MC-LR致癌作用的关键功能性LncRNA；采用cDNA转染和siRNA技术正、反向干预上述LncRNA，观察其效应，阐明其作用机制；并检测广西肝癌高/低发地区人群MC-LR暴露水平以及外周血、肝癌组织LncRNA表达水平，判断其作为MC-LR相关肝癌的早期诊断标志物之价值，为肝癌的早期预防和控制提供科学依据。

Microcystin-LR (MC-LR), the most important toxin in cyanobacteria-polluted water, was reported to be responsible for the increased incidence of hepatocellular carcinoma. However, the mechanism of its carcinogenic action remains undetermined. Results from our preliminary experiment have found that the long non-coding RNA (LncRNA) H19, HULC and HOTAIR displayed up-regulated expression while MEG3 and AFAP1-AS1 were down-regulated in malignant transformed human hepatocyte cell line induced by MC-LR. We speculated that LncRNA may be involved in hepatocarcinogenesis induced by MC-LR. In order to test the hypotheses, MC-LR is initially chosen to establish a malignant transformation model in immortalized hepatocyte cell line. LncRNA expression array analysis was then conducted in the transformed cells, followed by validation of select LncRNA by quantitative real-time reverse transcription PCR, and to define the key functional LncRNA during the cell malignant transformation. Subsequently, the expression of LncRNA in the human hepatocyte cell line is down-regulated by siRNA transfection and up-regulated by cDNA transfection, in order to investigate the role and mechanism of LncRNA in MC-LR-induced cell malignant transformation. Further, the level of MC-LR exposure, LncRNA expression of peripheral blood and hepatocellular carcinoma tissue are measured among people from high- or low-incidence area of Guangxi, in order to judge the value of LncRNA as a biomarker for early diagnosis of MC-LR-related hepatocellular carcinoma and provide a basis for the primary prevention of hepatocellular carcinoma.