LncRNA-241 inhibits 1,2-Dichloroethane-induced hepatic apoptosis
LncRNA-241 inhibits 1,2-Dichloroethane-induced hepatic apoptosis
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LncRNA-241 抑制 1,2-二氯乙烷诱导的肝细胞凋亡
DOI：
10.1016/j.tiv.2019.104650
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发表时间：
2019
影响因子：
3.2
通讯作者：
Wang Qing
中科院分区：
文献类型：
--
作者：
Zeng Ni;Zhang Zhen;Jiang Hongmei;Li Ruobi;Chang Chong;Wang Fei;Xu D;an;Fan Qiming;Wang Ting;Xiao Yongmei;Chen Wen;Shan Zhixin;Huang Zhenlie;Wang Qing
氯代有机化学品1，2-二氯乙烷（1，2-DCE）广泛应用于工业生产过程中，过量接触可能导致肝脏损伤。1，2-DCE诱导肝毒性的机制尚未完全了解。大量研究表明，长链非编码RNA（long-non-codingRNA，lncRNA）在化学品毒性中起着关键作用。为了探讨lncRNA表达异常是否参与了1，2-DCE暴露介导的肝毒性，我们采用基因芯片技术检测了1，2-DCE诱导的小鼠肝毒性模型中lncRNA表达谱的变化。生物信息学分析表明，1，2-DCE暴露后lncRNA（lncRNA 241）表达下调，可能参与了1，2-DCE诱导的肝毒性。我们用1，2-DCE及其代谢产物2-氯乙酸（2-CA）处理AML 1,2细胞48 h，结果表明，产生的是2-CA而不是初级形式（1，体外干预研究表明，2-CA暴露后lncRNA 241表达的抑制导致抗凋亡作用的下调，而2-DCE暴露后lncRNA 241表达的下调导致抗凋亡作用的下调。相关因子胰岛素生长因子-1（Igf 1）在mRNA和蛋白水平上通过调节其共同靶点mmu-miR-451 a而促进肝细胞凋亡。这项研究提供了有价值的洞察lncRNA的作用，响应1，2-DCE诱导的肝细胞凋亡。
Chlorinated organic chemical 1,2-dichloroethane (1,2-DCE) is used widely in industrial production processes, and excessive exposure may lead to liver damage. The mechanisms underlying 1,2-DCE-induced hepatotoxicity are not fully understood. Numerous studies have demonstrated that long-non-coding RNAs (lncRNAs) play a pivotal role in the chemical-induced toxicity. To explore whether aberrant lncRNA expression is involved in hepatotoxicity mediated by 1,2-DCE exposure, we detected alterations of lncRNA expression profiling in a mouse model of 1,2-DCE-induced hepatotoxicity by microarray chip. Bioinformatic analysis indicated that a down-regulated lncRNA (lncRNA241) after 1,2-DCE exposure might be involved in 1,2-DCE-induced hepatotoxicity. We treated AML12 cells with 1,2-DCE and its metabolite 2-chloroacetic acid (2-CA) for 48 h, and the results revealed that it was 2-CA rather than primary form (1,2-DCE) that resulted in the decline of lncRNA241 expression in hepatocytes.In vitrointervention studies revealed that the repression of lncRNA241 expression after 2-CA exposure led to the down-regulation of anti-apoptosis-associated factor insulin growth factor-1 (Igf1) at mRNA and protein levels through modulation of their common target mmu-miR-451a, which promoted hepatic apoptosis. This study provides valuable insight into the role of lncRNAs in response to hepatocyte apoptosis induced by 1,2-DCE.