• World Neurosurg · Apr 2020

    miR-195 functions as a tumor suppressor by directly targeting FASN in malignant meningioma.

    • Lai-Rong Song, Da Li, Jian-Cong Weng, Cheng-Bei Li, Liang Wang, Zhen Wu, and Jun-Ting Zhang.
    • Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Department of Neuro-Oncology, China National Clinical Research Center for Neurological Diseases, Beijing, China; Department of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China; Department of Cancer Biology, Beijing Key Laboratory of Brain Tumor, Beijing, China.
    • World Neurosurg. 2020 Apr 1; 136: e355-e364.

    ObjectiveMeningiomas are among the most common primary intracranial tumors. Up to 20% of cases will show increased malignancy at histological examination (World Health Organization grade II or III). Effective pharmacotherapy, except for radiotherapy, is lacking. Therefore, it is necessary to study the pathogenesis of malignant meningioma to provide more treatment strategies.MethodsRNA sequencing and micro-RNA (miRNA) microarray detection were applied to identify differentially expressed messenger RNAs (mRNAs) and miRNAs in benign and malignant meningioma. The miRDB and TargetScan databases were used to predict the potential interaction between miRNAs and mRNAs. A proliferation assay was used to evaluate the cell growth. A wound healing assay and Transwell assay were performed to assess the cell migration and invasion abilities, respectively. The interaction between miRNA and mRNA was identified using a luciferase reporter assay.ResultsWe found fatty acid synthase (FASN) was significantly upregulated in malignant meningioma compared with benign meningioma. Knockdown of FASN significantly inhibited proliferation, migration, and invasion of IOMM-Lee cells. Moreover, miR-195 was verified to directly target FASN using a luciferase reporter assay. Upregulation of miR-195 also significantly inhibited proliferation, migration, and invasion of IOMM-Lee cells. Furthermore, we performed bioinformatics analysis to predict the competing endogenous RNAs (ceRNAs) and found that NUP210, SPIRE2, SLC7A1, and DMTN might function as ceRNAs of FASN by sponging miR-195 in meningioma.ConclusionsOur results have suggested a tumor suppressive role for miR-195 in the tumorigenesis and progression of malignant meningioma by targeting FASN. In addition, NUP210, SPIRE2, SLC7A1, and DMTN might act as ceRNAs to regulate FASN expression by sponging miR-195.Copyright © 2020 Elsevier Inc. All rights reserved.

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