微囊藻毒素-LR（MCLR）是水华水体产生的有毒藻类毒素，流行病学调查显示广西肝癌的高发与MCLR暴露有关。课题组前期研究发现MCLR诱导细胞恶性转化时，谷氨酰半胱氨酸连接酶的催化亚基（GCLC）的表达和功能低下，长链非编码RNA lnc-GCLC-1和环状RNA has-circ-GCLC-overlap.1（circ-GCLC）表达下调，推测lnc-GCLC-1和circ-GCLC可能共同调控GCLC的表达而参与MCLR的致癌效应。本课题拟通过肝细胞恶性转化模型，动态观察细胞中lnc-GCLC-1、circ-GCLC与GCLC表达、氧化应激水平的变化；采用cDNA转染和siRNA技术正/反、双向干预lnc-GCLC-1、circ-GCLC和GCLC的表达，探讨三者在MCLR致癌过程中的作用，并利用广西肝癌高/低发现场人群验证毒理学实验的发现，为进一步阐明MCLR的致癌机制提供科学依据。

Microcystin-LR (MCLR), the most important toxin in cyanobacteria-polluted water, was reported to be responsible for the increased incidence of hepatocellular carcinoma in Guangxi. Results from our preliminary experiment have found that the expression and function of catalytic subunit of glutamylcysteine ligase (GCLC) were decreased, and the expression levels of the long non-coding RNA lnc-GCLC-1 and circRNA has-circ-GCLC-overlap.1 (circ-GCLC) were downregulated in malignant transformed human hepatocyte cell line induced by MCLR. We speculated that LncRNA and circRNA may regulate synergistically GCLC reduction and liver cells malignant transformation induced by MCLR. In order to test the hypotheses, MCLR is initially chosen to establish a malignant transformation model in immortalized hepatocyte cell line. Alterations in the expression levels of lnc-GCLC-1, circ-GCLC and GCLC, as well as oxidative stress status are then examined in MCLR-transformed cells. Subsequently, the expression of lnc-GCLC-1, circ-GCLC and GCLC in the transformed cell is upregulated by cDNA transfection and downregulated by siRNA transfection, in order to determine the role of lnc-GCLC-1, circ-GCLC and GCLC in MCLR-induced malignant transformation. Further, epidemiological investigations are performed to verify the toxicological findings among people from high- or low-incidence area of Guangxi. The aims of this study are to define the roles of regulation of GCLC expression by lnc-GCLC-1 and circ-GCLC during MCLR-induced malignant transformation of liver cells, and provide the evidence needed to clarify the mechanisms of carcinogenesis and early biomarkers for MCLR exposure.