miR-155 is up-regulated in primary and secondary glioblastoma and promotes tumour growth by inhibiting GABA receptors
miR-155 is up-regulated in primary and secondary glioblastoma and promotes tumour growth by inhibiting GABA receptors
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DOI：
10.3892/ijo.2012.1420
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发表时间：
2012-07-01
影响因子：
5.2
通讯作者：
Marsigliante, Santo
中科院分区：
文献类型：
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作者：
D'Urso, Pietro I.;D'Urso, Oscar F.;Marsigliante, Santo
microRNA（miRNAs）的表达改变有助于癌症的发展和疾病的进展。与正常组织相比，恶性肿瘤和肿瘤细胞系具有广泛失调的miRNA表达。在这项研究中，我们研究了340哺乳动物的miRNA的表达谱在93例多形性胶质母细胞瘤（原发性和继发性胶质母细胞瘤肿瘤），通过DNA微阵列。我们发现，10个miRNA的表达谱可以区分原发性和继发性胶质母细胞瘤类型。此外，我们发现在原发性和继发性胶质母细胞瘤组织以及胶质母细胞瘤原代培养物中miR-155水平升高。我们假设γ-氨基丁酸A受体1（GABRA 1）是miR-155的靶点，并通过miRNA沉默研究了培养的胶质母细胞瘤细胞中miR-155上调与GABRA 1蛋白之间的相关性。我们发现，miR-155表达降低到正常水平恢复了GABRA 1的表达，使胶质母细胞瘤细胞对GABRA 1介导的抑制细胞增殖的信号敏感。总之，不同的miRNAs表达模式决定了原发性和继发性胶质母细胞瘤。miR-155的异常过表达有助于胶质母细胞瘤细胞的恶性表型，从而消除生长抑制。
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 gamma-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.