Melatonin triggers autophagic cell death by regulating RORC in Hodgkin lymphoma.
Melatonin triggers autophagic cell death by regulating RORC in Hodgkin lymphoma.
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DOI：
10.1016/j.biopha.2020.109811
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发表时间：
2020-01
期刊：
影响因子：
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通讯作者：
Gege Yan;Hong Lei;Mingyu He;Rui Gong;Yang Wang;Xiaoqi He;Guanghui Li;Ping Pang;Xin Li-
中科院分区：
文献类型：
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作者：
Gege Yan;Hong Lei;Mingyu He;Rui Gong;Yang Wang;Xiaoqi He;Guanghui Li;Ping Pang;Xin Li-
褪黑激素（Melatonin，Mel）通过调节多种信号通路参与多种细胞功能。我们首次研究了Mel通过抑制细胞增殖和促进细胞凋亡发挥抗霍奇金淋巴瘤（HL）的作用。进一步的研究表明，Mel处理增加了LC 3-II的表达，降低了p62蛋白的表达，同时增加了自溶酶体的产生，表明Mel诱导了自噬的激活。然而，Mel与自噬抑制剂3-MA或CQ共同处理可加重Mel对HL细胞的损伤作用，这意味着自噬在此过程中起保护作用。此外，我们发现Mel处理增加了G蛋白偶联受体MT 2和视黄酸相关孤儿受体（RORs）的表达，如：RORA、RORB和RORC。而RORC在Mel处理的HL细胞中具有最高的增加。此外，RORC过表达诱导自噬激活。因此，Mel由于在HL中增加的RORC诱导的自噬水平而显示肿瘤抑制作用。
Melatonin (Mel) has been shown to involve in many essential cell functions via modulating many signaling pathways. We for the first time investigated that Mel exerted anti-tumor activities in Hodgkin lymphoma (HL) via inhibiting cell proliferation and promoting cell apoptosis. Further study revealed that Mel treatment increased expression of LC3-II and decreased p62 proteins with the enhanced production of autolysosome, indicating it induced activation of autophagy. Nevertheless, Mel treatment together with autophagy inhibitors 3-MA or CQ exacerbated the damage effect of Mel in HL cells, which means autophagy plays a protective role in this process. Furthermore, we found Mel treatment increased the expression of G protein-coupled receptors MT2 and retinoic acid-related orphan receptors (RORs), eg. RORA, RORB and RORC. While RORC has the highest increase in Mel treated HL cells. In addition, RORC overexpression induced autophagy activation. Therefore, Mel showed tumor-suppressive role due to an increased level of RORC induced autophagy in HL.