Melatonin inhibits proliferation and invasion via repression of miRNA-155 in glioma cells

作者:Gu, Junyi; Lu, Zhongsheng; Ji, Chenghong; Chen, Yuchao; Liu, Yuzhao; Lei, Zhe; Wang, Longqiang; Zhang, Hong-Tao*; Li, Xiangdong*
来源:Biomedicine & Pharmacotherapy, 2017, 93: 969-975.
DOI:10.1016/j.biopha.2017.07.010

摘要

Melatonin, an indolamine mostly synthesized in the pineal gland, exerts the anti-cancer effect by various mechanisms in glioma cells. Our previous study showed that miR-155 promoted glioma cell proliferation and invasion. However, the question of whether melatonin may inhibit glioma by regulating miRNAs has not yet been addressed. In this study, we found that melatonin (100 mu M, 1 mu M and 1 nM) significantly inhibited the expression of miR-155 in human glioma cell lines U87, U373 and U251. Especially, the lowest expression of miR-155 was detected in 1 mu M melatonin-treated glioma cells. Melatonin (1 mu M) inhibits cell proliferation of U87 by promoting cell apoptosis. Nevertheless, melatonin had no effect on cell cycle distribution of U87 cells. Moreover, U87 cells treated with 1 mu M melatonin presented significantly lower migration and invasion ability when compared with control cells. Importantly, melatonin inhibited c-MYB expression, and c-MYB knockdown reduced miR-155 expression and migration and invasion in U87 cells. Taken together, for the first time, our findings show that melatonin inhibits miR-155 expression and thereby represses glioma cell proliferation, migration and invasion, and suggest that melatonin may downregulate the expression of miR-155 via repression of c-MYB. This will provide a theoretical basis for revealing the anti-glioma mechanisms of melatonin.