Department of Biological and Environmental Sciences and Technologies, DISTEBA, University of Salento, I-73100 Lecce, Italy.
Int J Oncol. 2012 Jul;41(1):228-34. doi: 10.3892/ijo.2012.1420. Epub 2012 Mar 28.
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.
miRNAs（微 RNA）的表达改变既有助于癌症的发展，也有助于疾病的进展。与正常组织相比，恶性肿瘤和肿瘤细胞系中 miRNA 的表达广泛失调。在这项研究中，我们通过 DNA 微阵列研究了 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）中 340 种哺乳动物 miRNA 的表达谱。我们发现 10 种 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（GABRA1）是 miR-155 的靶标，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 GABRA1 蛋白之间的相关性。我们发现，将 miR-155 的表达降低到正常水平会恢复 GABRA1 的表达，使胶质母细胞瘤细胞对通过 GABRA1 抑制细胞增殖的信号敏感。总之，不同 miRNA 的表达模式特征化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，消除生长抑制。
