miR-155 is up-regulated in primary and secondary glioblastoma and promotes tumour growth by inhibiting GABA receptors

Pietro I. D'Urso, Oscar F. D'Urso, Carlo Storelli, Massimo Mallardo, Cosimo Damiano Gianfreda, Antonio Montinaro, Antonia Cimmino, Caliandro Pietro, Santo Marsigliante

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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.

Original languageEnglish
Pages (from-to)228-234
Number of pages7
JournalInternational Journal of Oncology
Volume41
Issue number1
DOIs
Publication statusPublished - Jul 2012

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Keywords

  • Gene expression
  • Glioblastoma
  • Microarray
  • MicroRNA
  • Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

D'Urso, P. I., D'Urso, O. F., Storelli, C., Mallardo, M., Gianfreda, C. D., Montinaro, A., Cimmino, A., Pietro, C., & Marsigliante, S. (2012). miR-155 is up-regulated in primary and secondary glioblastoma and promotes tumour growth by inhibiting GABA receptors. International Journal of Oncology, 41(1), 228-234. https://doi.org/10.3892/ijo.2012.1420