Resveratrol-induced apoptosis is associated with regulating the miR-492/CD147 pathway in malignant melanoma cells
Resveratrol-induced apoptosis is associated with regulating the miR-492/CD147 pathway in malignant melanoma cells
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白藜芦醇诱导的细胞凋亡与调节恶性黑色素瘤细胞中的 miR-492/CD147 通路相关
DOI：
10.1007/s00210-020-01981-4
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发表时间：
2020-10-03
影响因子：
3.6
通讯作者：
Wu, Lisha
中科院分区：
文献类型：
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作者：
Zhao, Shuang;Tang, Ling;Wu, Lisha
白藜芦醇（Resveratrol，RES）是一种天然植物抗毒素，通过其促细胞凋亡活性对多种肿瘤具有抗肿瘤作用。我们的目的是确定RES通过调节miR-492导致CD 147表达降低来诱导黑素瘤细胞凋亡。我们通过RES在不同浓度和时间点处理A375和SK-MEL-28黑色素瘤细胞。结果表明，经RES处理后，A375和SK-MEL-28的抑制率显著增加。流式细胞仪检测细胞凋亡，Western blotting检测凋亡相关蛋白PARP、Caspase-3、Bcl-2、Bax的表达。同时分析miR-492和CD 147的表达。我们发现RES显著诱导黑色素瘤细胞凋亡，同时沿着miR-492的上调和CD 147表达的抑制。此外，荧光素酶报告基因活性的检测证实了miR-492可以靶向CD 147 mRNA，并且在细胞中转染模拟miR-492可以降低CD 147的表达。我们还通过在黑色素瘤细胞中使用miR-492抑制剂进行了挽救实验。结果表明，RES诱导黑色素瘤细胞凋亡的能力可通过抑制miR-492的表达而减弱，从而导致CD 147的增加。最后，我们确定RES诱导的黑色素瘤细胞凋亡的作用至少部分与其调节miR-492/CD 147通路的能力相关。
Resveratrol (RES) as a natural phytoalexin has anti-tumor effects on various cancers through its pro-apoptotic activities. Our aim was to determine that RES induces apoptosis in melanoma cells by regulating miR-492 resulting in decreased CD147 expression. We treated A375 and SK-MEL-28 melanoma cells via RES at different concentrations and time-points. The results have shown that the inhibition rate of A375 and SK-MEL-28 was significantly increased after RES treatment. Subsequently, we investigated cell apoptosis by flow cytometry, as well as detected apoptotic-associated proteins including PARP, Caspase-3, Bcl-2, and Bax by western blotting. Meanwhile, the expression of miR-492 and CD147 was analyzed. We found that RES remarkably induces apoptosis in melanoma cells, along with an upregulation of miR-492 and the inhibition of CD147 expression. Furthermore, the detection of luciferase reporter activity confirmed that miR-492 could target CD147 mRNA, and transfected with mimic miR-492 in cells reduced CD147 expression. We also performed the rescued experiment by using a miR-492 inhibitor in melanoma cells. The results showed that the ability of induced apoptosis by RES in melanoma cells was to be attenuated via inhibiting miR-492 expression resulting in CD147 augment. Finally, we determined that the effect of RES-induced apoptosis in melanoma cells is associated with, at least in part, its ability to regulate the miR-492/CD147 pathway.