Expression of PRMT5 correlates with malignant grade in gliomas and plays a pivotal role in tumor growth in vitro.

Expression of PRMT5 correlates with malignant grade in gliomas and plays a pivotal role in tumor growth in vitro.
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DOI:
10.1007/s11060-014-1419-0
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发表时间:
2014-05
影响因子:
3.9
通讯作者:
Nabors, L. Burt
Nabors, L. Burt
中科院分区:
医学2区
文献类型:
--
作者:
Han, Xiaosi;Li, Rong;Zhang, Wenbin;Yang, Xiuhua;Wheeler, Crystal G.;Friedman, Gregory K.;Province, Paula;Ding, Qiang;You, Zhiying;Fathallah-Shaykh, Hassan M.;Gillespie, G. Yancey;Zhao, Xinyang;King, Peter H.;Nabors, L. Burt

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蛋白质精氨酸甲基转移酶5(PRMT 5)催化组蛋白以及其他蛋白质上ω-NG、NG对称二甲基精氨酸残基的形成。这些修饰在细胞分化和肿瘤细胞生长中起重要作用。然而,PRMT 5在人神经胶质瘤细胞中的作用尚未被表征。在这项研究中,我们通过免疫组织化学评估了PRMT 5在对照脑、WHO II级星形细胞瘤、间变性星形细胞瘤和多形性胶质母细胞瘤(GBM)中的蛋白表达谱。PRMT 5在对照脑组织和低级别星形细胞瘤中的胶质细胞中是低的。其表达与恶性进展平行增加,并且在GBM中高度表达。小发夹RNA敲低PRMT 5可引起p-ERK 1/2的改变,并显著抑制胶质瘤细胞的克隆形成能力和生存力。这些发现表明PRMT 5是胶质瘤肿瘤恶性进展的标志物,并在肿瘤生长中起关键作用。
Protein arginine methyltransferase 5 (PRMT5) catalyzes the formation of ω-NG,N'G-symmetric dimethylarginine residues on histones as well as other proteins. These modifications play an important role in cell differentiation and tumor cell growth. However, the role of PRMT5 in human glioma cells has not been characterized. In this study, we assessed protein expression profiles of PRMT5 in control brain, WHO grade II astrocytomas, anaplastic astrocytomas, and glioblastoma multiforme (GBM) by immunohistochemistry. PRMT5 was low in glial cells in control brain tissues and low grade astrocytomas. Its expression increased in parallel with malignant progression, and was highly expressed in GBM. Knockdown of PRMT5 by small hairpin RNA caused alterations of p-ERK1/2 and significantly repressed the clonogenic potential and viability of glioma cells. These findings indicate that PRMT5 is a marker of malignant progression in glioma tumors and plays a pivotal role in tumor growth.
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