铅暴露通过Merlin-mTOR信号通路促脑膜瘤细胞增殖及迁移侵袭

Lead Exposure Promotes the Proliferation,Migration and Invasion of Meningioma Cells via the Merlin-mTOR Signaling Pathway

铅(Pb)毒性是影响全球数百万人的公共卫生问题,临床研究发现脑膜瘤的重要危险因素是铅暴露。同时在脑膜瘤患者体内常能发现由NF2基因编码的Merlin蛋白缺失。但是铅暴露如何调节脑膜瘤细胞的发生发展目前研究仍无定论。本研究旨在分析铅暴露对脑膜瘤细胞的增殖、细胞体积、迁移侵袭能力的影响以及其潜在分子机制。结果显示,醋酸铅可抑制脑膜瘤细胞IOMM-Lee的Merlin蛋白表达、促进细胞的增殖和迁移侵袭能力、mTOR分子磷酸化增加,而Merlin蛋白外源过表达则可逆转醋酸铅介导的细胞增殖迁移侵袭能力增加、 mTOR磷酸化分子增加。该结果提示,铅暴露可通过Merlin-mTOR信号通路促进脑膜瘤细胞IOMM-Lee的增殖和迁移侵袭。

Lead toxicity is a public health problem affecting millions of people worldwide.Clinical studies have shown that lead exposure is a risk factor for meningioma.Meanwhile,NF2(neurofibromatosis type 2) deficit is common in meningioma patients.Nevertheless,the mechanism of lead exposure in meningioma is not clear.This study aims to clarify the effect of lead exposure on the proliferation,migration and invasion of meningioma cells,and its potential molecular mechanism.The results showed that lead acetate exposure inhibited the expression of Merlin,promoted cell proliferation and enhanced cell migration and invasion,and increased the phosphorylation levels of mTOR in IOMM-Lee cells.Meanwhile,overexpression of Merlin could reverse the above effects.These results suggest that lead exposure promotes the proliferation,migration,and invasion of meningioma cells,which probably is mediated by the Merlin-mTOR signaling pathway.