MiRNA expression profiling in human gliomas: upregulated miR-363 increases cell survival and proliferation
MiRNA expression profiling in human gliomas: upregulated miR-363 increases cell survival and proliferation
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DOI：
10.1007/s13277-016-5273-x
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发表时间：
2016-10-01
期刊：
影响因子：
--
通讯作者：
Aguennouz, M'hammed
中科院分区：
文献类型：
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作者：
Conti, Alfredo;Romeo, Sara G.;Aguennouz, M'hammed
microRNA (miRNA) 在神经胶质瘤生物学中的作用日益得到认可。为了研究不同恶性程度的神经胶质瘤的恶性特征的调控机制，我们分析了人类 I-IV 级肿瘤样本和原代神经胶质瘤细胞培养物中的 miRNA 表达谱。使用多重实时 PCR 来分析一组世界卫生组织 (WHO) I 级（毛细胞性星形细胞瘤）、II 级（弥漫性纤维性星形细胞瘤）和 IV 级（多形性胶质母细胞瘤）星形细胞肿瘤和原代神经胶质瘤细胞培养物中的 miRNA 表达。原代神经胶质瘤细胞培养物用于评估特定 miRNA 和 miRNA 抑制剂转染的效果。 miRNA 微阵列显示一组 miRNA 在所有神经胶质瘤样本中持续上调。 miR-363在所有肿瘤标本和细胞系中均上调，其表达与肿瘤分级相关。用 miR-363 特异性抑制剂转染神经胶质瘤细胞可增加肿瘤抑制生长相关蛋白 43 (GAP-43) 的表达水平。转染 miR-363 会诱导细胞存活，而抑制 miR-363 会显着降低神经胶质瘤细胞的活力。此外，抑制 miRNA-363 会诱导 AKT、cyclin-D1、基质金属蛋白酶 (MMP)-2、MMP-9 和 Bcl-2 的下调以及 caspase 3 的上调。 总之，这些数据表明 miR-363 的上调可能在恶性胶质瘤特征中发挥作用。
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.