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

作　　者：王筝[1] 沈晓华[2] 朱佳[3] WANG Zheng;SHEN Xiao-Hua;ZHU Jia(Clinical Research Institute,Jiaxing University Medical College,Jiaxing 314001,Zhejiang,China;Department of Laboratory Medicine and Pathology,Jiaxing Hospital of Traditional Chinese Medicine,Jiaxing 314001,Zhejiang,China;Department of Molecular Pathology,Jiaxing University Medical College,Jiaxing 314001,Zhejiang,China)

机构地区：[1]嘉兴学院医学院临床研究所,浙江嘉兴314001 [2]嘉兴市中医医院检验与病理科,浙江嘉兴314001 [3]嘉兴学院医学院分子病理学实验室,浙江嘉兴314001

出　　处：《中国生物化学与分子生物学报》2023年第2期234-243,共10页Chinese Journal of Biochemistry and Molecular Biology

基　　金：嘉兴市科技计划项目(No.2021AY10049)资助。

摘　　要：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.

关 键 词：铅暴露 脑膜瘤 IOMM-Lee细胞 MERLIN MTOR S6 

分 类 号：R114[医药卫生—卫生毒理学]