title: MiRNA expression profiling in human gliomas: upregulated miR-363 increases cell survival and proliferation.
abstract: The role of microRNAs (miRNAs) in glioma biology is increasingly recognized. To investigate the regulatory mechanisms governing the malignant signature of gliomas with different grades of malignancy, we analyzed miRNA expression profiles in human grade I-IV tumor samples and primary glioma cell cultures. Multiplex real-time PCR was used to profile miRNA expression in a set of World Health Organization (WHO) grade I (pilocytic astrocytoma), II (diffuse fibrillary astrocytoma), and IV (glioblastoma multiforme) astrocytic tumors and primary glioma cell cultures. Primary glioma cell cultures were used to evaluate the effect of transfection of specific miRNAs and miRNA inhibitors. miRNA microarray showed that a set of miRNAs was consistently upregulated in all glioma samples. miR-363 was upregulated in all tumor specimens and cell lines, and its expression correlated with tumor grading. The transfection of glioma cells with the specific inhibitor of miR-363 increased the expression level of tumor suppressor growth-associated protein 43 (GAP-43). Transfection of miR-363 induced cell survival, while inhibition of miR-363 significantly reduced glioma cell viability. Furthermore, miRNA-363 inhibition induced the downregulation of AKT, cyclin-D1, matrix metalloproteinase (MMP)-2, MMP-9, and Bcl-2 and upregulation of caspase 3. Together, these data suggest that the upregulation of miR-363 may play a role in malignant glioma signature.
authors: Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy. alfredo.conti@unime.it.
authors: Alfredo
authors: A
authors: Conti
authors: Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
authors: Sara G
authors: SG
authors: Romeo
authors: Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
authors: Annamaria
authors: A
authors: Cama
authors: Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
authors: Domenico
authors: D
authors: La Torre
authors: Department of Adulthood and Childhood Pathology "G. Barresi", University of Messina, Messina, Italy.
authors: Valeria
authors: V
authors: Barresi
authors: Department of Adulthood and Childhood Pathology "G. Barresi", University of Messina, Messina, Italy.
authors: Gaetana
authors: G
authors: Pezzino
authors: Department of Adulthood and Childhood Pathology "G. Barresi", University of Messina, Messina, Italy.
authors: Chiara
authors: C
authors: Tomasello
authors: Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
authors: Salvatore
authors: S
authors: Cardali
authors: Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
authors: Filippo F
authors: FF
authors: Angileri
authors: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors: Francesca
authors: F
authors: Polito
authors: Department of Adulthood and Childhood Pathology "G. Barresi", University of Messina, Messina, Italy.
authors: Guido
authors: G
authors: Ferlazzo
authors: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors: Rosamaria
authors: R
authors: Di Giorgio
authors: Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
authors: Antonino
authors: A
authors: Germanò
authors: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors: M'hammed
authors: M
authors: Aguennouz
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D049109:Cell Proliferation; D005500:Follow-Up Studies; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D020827:rap1 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D019922:GAP-43 Protein; C574861:MIRN363 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D012097:Repressor Proteins; C486544:HDAC9 protein, human; D006655:Histone Deacetylases; D020827:rap1 GTP-Binding Proteins
keywords: Astrocytoma; Gap-43; Glioblastoma multiforme; miRNA microarray; miRNA-363