Effects of the Tight Junction Protein CLDN6 on Cell Migration and Invasion in High-Grade Meningioma.

Anqiang Yang, Xiaobin Yang, Jianqiu Wang, Xiaojun Wang, Hegang Wu, Li Fan, Hao Li, Jiangtao Li

World neurosurgery 2021 Jul

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Meningioma is a common tumor of the central nervous system, and malignant meningioma is highly aggressive and frequently recurs after surgical resection. Claudin 6 (CLDN6) is involved in cell proliferation, migration, and invasion and plays a role in maintaining tight junctions between cells and obstructing the movement of cells to neighboring tissues. In the present study, we evaluated the effect of tight junction protein CLDN6 expression levels on meningioma invasiveness using silencing and overexpression constructs in both in vitro and in vivo models. The expression of CLDN6 at the mRNA and protein levels was measured using quantitative reverse transcription polymerase chain reaction and Western blot assays. We found that CLDN6 was expressed at higher levels in normal meningeal tissue and cell samples. Next, vectors with silenced and overexpressed CLDN6 were successfully established, and the expression of CLDN6 mRNA and protein in the IOMM-Lee and CH157-MN cell lines was downregulated after transfection with siRNA-CLDN6 and upregulated by transfection of the entire CLDN6 sequence vector. An in vitro assay revealed that abrogation of CLDN6 expression added to the capacity for tumor migration and invasion relative to the overexpression of CLDN6. In addition to the in vitro evidence, we observed a significant increase in tumor growth and invasion-associated gene expression, including matrix metalloproteinase-2, matrix metalloproteinase-9, vimentin, and N-cadherin, after silencing CLDN6 expression in vivo. CLDN6 might play an important role in meningioma migration and invasion and, thus, might serve as a novel diagnostic and/or prognostic biomarker and as a potential therapeutic target. Copyright © 2021 Elsevier Inc. All rights reserved.

Citation

Anqiang Yang, Xiaobin Yang, Jianqiu Wang, Xiaojun Wang, Hegang Wu, Li Fan, Hao Li, Jiangtao Li. Effects of the Tight Junction Protein CLDN6 on Cell Migration and Invasion in High-Grade Meningioma. World neurosurgery. 2021 Jul;151:e208-e216