ADAM12 Silencing Mediated by FOXC2 Represses Meningioma Progression Through Inactivating the JAK1/STAT3/VEGFA Pathway

Abstract

Meningioma is a prevalently intracranial tumor, and the malignant type is aggressive with high recurrence. A Disintegrin and Metalloprotease 12 (ADAM12) is a common oncogene and differentially expressed in meningioma. However, its roles and mechanisms in meningioma development remain obscure. The differentially expressed genes in meningioma were analyzed by GEO (GSE77259 and GSE43290) datasets and weighted gene co-expression network analysis (WGCNA) based on GSE16581. ADAM12 expression was measured via qRT-PCR and western blot. The correlation between ADAM12 and FOXC2 was predicted through JASPER tool and identified via luciferase reporter analysis. Cell proliferation, migration and invasion were investigated using CCK-8, EdU, transwell assays. The JAK1/STAT3/VEGFA signaling was activated by IL-6, and analyzed via western blot. The differentially expressed ADAM12 in meningioma was screened by WGCNA and GEO analyses. ADAM12 silencing repressed meningioma cell proliferation, and decreased migration and invasion. The transcription factor FOXC2 expression was enhanced in meningioma based on GSE77259 and GSE43290 datasets, and positively induced ADAM12 transcription. The JAK1/STAT3/VEGFA signaling was inactivated due to ADAM12 silencing and activated via IL-6. Upregulation of FOXC2 promoted cell proliferation, migration and invasion, and these effects were reversed by silencing ADAM12. ADAM12 knockdown mediated via FOXC2 silencing restrained proliferation, migration and invasion of meningioma cells through inactivating the JAK1/STAT3/VEGFA pathway.