M6A RNA Methylation Regulator HNRNPC Contributes to Tumorigenesis and Predicts Prognosis in Glioblastoma Multiforme.

M6A RNA Methylation Regulator HNRNPC Contributes to Tumorigenesis and Predicts Prognosis in Glioblastoma Multiforme.
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M6A RNA 甲基化调节因子 HNRNPC 有助于多形性胶质母细胞瘤的肿瘤发生并预测预后

DOI:
10.3389/fonc.2020.536875
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发表时间:
2020
影响因子:
4.7
通讯作者:
Lv QL
Lv QL
中科院分区:
医学3区
文献类型:
--
作者:
Wang LC;Chen SH;Shen XL;Li DC;Liu HY;Ji YL;Li M;Yu K;Yang H;Chen JJ;Qin CZ;Luo MM;Lin QX;Lv QL

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多形性胶质母细胞瘤(GBM)是恶性程度最高的胶质瘤,死亡率很高。 N6-甲基腺苷 (m6A) RNA 甲基化在肿瘤中发挥着越来越重要的作用。目前的研究旨在确定 GBM 中 m6A RNA 甲基化调节因子的功能。我们利用 TCGA 数据库评估了这些监管机构的差异、相互作用和相关性。 HNRNPC、WTAP、YTHDF2 和 YTHDF1 在 GBM 中显着上调。为了探索 GBM 中调节因子的表达特征,我们通过共识簇定义了两个亚组。 HNRNPC、WTAP 和 YTHDF2 在具有良好总生存 (OS) 的 cluster2 中显着上调。为了研究调节因子的预后价值,我们使用lasso cox回归算法根据HNRNPC、ZC3H13和YTHDF2的表达来筛选独立的预后风险特征。低危组和高危组的预后特征存在显着差异(P < 0.05),具有预测预后的意义(曲线下面积(AUC)= 0.819)。此外,我们使用蛋白质印迹、RT-PCR和免疫组化染色来验证HNRNPC的表达与胶质瘤的恶性和发展相关。同样,HNRNPC的高表达具有良好的预后。总之,HNRNPC 是 GBM 恶性进展的重要参与者,可能对预后有价值。
Glioblastoma multiforme (GBM) is the most malignant glioma with a high death rate. N6-methyladenosine (m6A) RNA methylation plays an increasingly important role in tumors. The current study aimed to determine the function of the regulators of m6A RNA methylation in GBM. We evaluated the difference, interaction, and correlation of these regulators with TCGA database. HNRNPC, WTAP, YTHDF2 and, YTHDF1 were significantly upregulated in GBM. To explore the expression characteristics of regulators in GBM, we defined two subgroups through consensus cluster. HNRNPC, WTAP, and YTHDF2 were significantly upregulated in the cluster2 which had a good overall survival (OS). To investigate the prognostic value of regulators, we used lasso cox regression algorithm to screen an independent prognostic risk characteristic based on the expression of HNRNPC, ZC3H13, and YTHDF2. The prognostic feature between the low and high-risk groups was significantly different (P < 0.05), which could predict significance of prognosis (area under the curve (AUC) = 0.819). Moreover, we used western blot, RT-PCR, and immunohistochemical staining to verify the expression of HNRNPC was associated with malignancy and development of gliomas. Similarly, the high expression of HNRNPC had a good prognosis. In conclusion, HNRNPC is a vital participant in the malignant progression of GBM and might be valuable for prognosis.
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