miR-153-5p suppresses the proliferation, invasion and migration of malignant meningioma via the MEK/ERK signaling pathway by targeting GAB1

Abstract

Aims:This study aimed to determine the role and correlation of miR-153-5p and GAB1 in the proliferation, invasion and migration of malignant meningioma. Background:Meningiomas are the most common primary intracranial tumor in adults.For meningioma, the only effective treatment and targeted therapy is excision and radiotherapy.However,some meningiomas are prone to recurring due to specific disease sites or an invasion of blood vessels and nerves, and the prognosis is poor.To discover biomarkers and develop targeted therapies, it is necessary to better understand meningioma oncogenesis. Methods:Human meningioma tissues were collected from patients diagnosed in pathological examinations. In addition, human malignant meningioma cell lines IOMM-Lee was included. Quantitative RT-PCR was used to detect the miR-153-5p and GAB1 level in the clinical tissues and cell lines.Immunohistochemistry was used to detect GAB1 expression.The specific binding site between miR-153-5p and GAB1 was predicted using bioinformatics, and dual luciferase assay was used to confirm their specific binding relationship. In IOMM-Lee, miR-153-5p was artificially overexpressed or suppressed and target gene expression GAB1 was blocked by siRNA. Cell proliferation, invasion and migration were measured using CCK-8,Transwell and Wound-healing assays.The activity of the MEK/ERK pathway was evaluated by detecting the key factors through Western blotting. Results:We found that miR-153-5p expression was low and GAB1 mRNA was high in meningioma tissues and IOMM-Lee cell lines. GAB1 is a direct target gene of miR-153-5p.Both miR-153-5p overexpression and GAB1 silencing inhibited malignant meningioma cells proliferation, migration and invasion,and GAB1 silencing partially blocked the effect of miR-153-5p silencing in these respects.We also confirmed that miR-153-5p might regulate MEK/ERK pathway activation by inhibiting GAB1 expression. Conclusions: miR-153-5p suppresses the proliferation, invasion and migration of malignant meningioma via the MEK/ERK signaling pathway by targeting GAB1, defining miR-153-5p and GAB1 as a potential target for the diagnosis and treatment of malignant meningioma.