title: miR-155 is up-regulated in primary and secondary glioblastoma and promotes             tumour growth by inhibiting GABA receptors.
abstract: An altered expression of microRNAs (miRNAs) contributes both to the development of cancer and to the progression of the disease. Malignant tumours and tumour cell lines have widespread deregulated expressions of miRNAs compared to normal tissues. In this study, we investigated the expression profiles of 340 mammalian miRNAs in 93 cases of multiform glioblastoma (primary and secondary glioblastoma tumours), by means of DNA microarrays. We show that the expression profiles of 10 miRNAs can distinguish primary from secondary glioblastoma types. Moreover, we found elevated miR-155 levels in primary and secondary glioblastoma tissues as well as in glioblastoma primary cultures. We hypothesised that γ-aminobutyric acid A receptor 1 (GABRA1) is a miR-155 target, and studied the correlation between miR-155 up-regulation and the GABRA1 protein in cultured glioblastoma cells by miRNA silencing. We show that a decrease in miR-155 expression to normal levels restores the expression of GABRA1, making glioblastoma cells sensitive to signals that inhibit cell proliferation mediated by GABRA1. In conclusion, the expression patterns of different miRNAs characterise primary and secondary glioblastomas. The aberrant overexpression of miR-155 contributes to the malignant phenotype of glioblastoma cells removing growth inhibition.
authors.affiliation: Department of Biological and Environmental Sciences and Technologies, DISTEBA, University of Salento, I-73100 Lecce, Italy.
authors.forename: Pietro I
authors.initials: PI
authors.lastname: D'Urso
authors.forename: Oscar F
authors.initials: OF
authors.lastname: D'Urso
authors.forename: Carlo
authors.initials: C
authors.lastname: Storelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Mallardo
authors.forename: Cosimo Damiano
authors.initials: CD
authors.lastname: Gianfreda
authors.forename: Antonio
authors.initials: A
authors.lastname: Montinaro
authors.forename: Antonia
authors.initials: A
authors.lastname: Cimmino
authors.forename: Caliandro
authors.initials: C
authors.lastname: Pietro
authors.forename: Santo
authors.initials: S
authors.lastname: Marsigliante
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000175:diagnosis / Q000378:metabolism* / Q000556:secondary; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C546240:GABRA1 protein, human; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D011963:Receptors, GABA-A