Regulation of Microcystin-LR-Induced DNA Damage by miR-451a in HL7702 Cells
Regulation of Microcystin-LR-Induced DNA Damage by miR-451a in HL7702 Cells
复制标题
miR-451a 对 HL7702 细胞中微囊藻毒素-LR 诱导的 DNA 损伤的调节
DOI：
10.3390/toxins11030164
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发表时间：
2019-03-15
期刊：
影响因子：
4.2
通讯作者：
Yang, Fei
中科院分区：
文献类型：
--
作者：
Chen, Lv;Yang, Shu;Yang, Fei
微囊藻毒素-LR是由有害蓝藻产生的一种环状七肽肝毒素。我们在前期的研究中发现，正常人肝细胞HL 7702暴露于微囊藻毒素-LR（MC-LR）后，一组含有miR-451 a的microRNA发生了显著变化。然而，miR-451 a在MC-LR诱导的肝毒性中的作用尚不清楚。本研究旨在研究5或10 μM MC-LR处理后miR-451 a对HL 7702细胞的影响。彗星实验表明MC-LR能影响HL 7702细胞的Olive尾矩（OTM）。miR-451 a的表达显著抑制MC-LR诱导的DNA损伤和γ-H2 AX蛋白表达水平。此外，过表达miR-451 a抑制MC-LR处理后细胞中p-AKT 1蛋白的表达水平。这些结果表明，miR-451 a可能通过下调p-AKT 1的表达，对MC-LR诱导的DNA损伤起到保护作用，为MC-LR诱导的肝损伤的诊断和治疗提供了新的线索。
Microcystin-LR is a cyclic heptapeptide hepatotoxin produced by harmful cyanobacteria. A panel of microRNAs containing miR-451a were found to be significantly changed in normal human liver cells HL7702 after exposure to microcystin-LR (MC-LR) in our previous study. However, the functions of miR-451a in hepatotoxicity induced by MC-LR remained unclear. The study aimed to investigate the impacts of miR-451a in HL7702 cells following treatment with 5 or 10 μM MC-LR. The comet assay indicated that MC-LR can influence Olive tail moment (OTM) in HL7702 cells. Furthermore, increase of miR-451a significantly repressed DNA damage and the protein expression level of γ-H2AX induced by MC-LR. Moreover, over-expression of miR-451a inhibited the expression level of p-AKT1 protein in cells following treatment by MC-LR. These results showed that miR-451a may protect from MC-LR-induced DNA damage by down-regulating the expression of p-AKT1, which provides new clues for the diagnosis and therapy policies for liver damage induced by MC-LR.