Role of KCNB1 in the prognosis of gliomas and autophagy modulation.
Role of KCNB1 in the prognosis of gliomas and autophagy modulation.
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KCNB1 在神经胶质瘤预后和自噬调节中的作用
DOI：
10.1038/s41598-017-00045-7
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发表时间：
2017-02-08
影响因子：
4.6
通讯作者：
Zhang SZ
中科院分区：
文献类型：
--
作者：
Wang HY;Wang W;Liu YW;Li MY;Liang TY;Li JY;Hu HM;Lu Y;Yao C;Ye YY;Wang YZ;Zhang SZ
越来越多的证据表明，离子通道基因在胶质瘤的发展过程中起着重要作用。然而，离子通道基因影响胶质瘤进展的机制尚不完全清楚。我们从三个数据集(CGGA、GSE16011和伦勃朗)中确定KCNB1是一个新的离子基因，与胶质瘤患者的恶性进展和有利的总体生存(OS)和无进展生存(PFS)相关。此外，我们还鉴定了KCNB1的一种新的功能，即自噬诱导伴随着增加胶质瘤细胞的凋亡和减少其增殖和侵袭。KEGG途径分析和体外研究表明，ERK通路参与了KCNB1介导的自噬调节，选择性ERK1/2抑制剂(U0126)或siERK1/2抑制KCNB1诱导的自噬证实了这一点。在活体研究中，KCNB1诱导自噬的同时抑制肿瘤生长和提高生存率。总体而言，我们的研究将KCNB1定义为一种新的胶质瘤预后因子，它通过自噬诱导发挥其肿瘤抑制功能。
Increasing evidence suggests that ion channel genes play an important role in the progression of gliomas. However, the mechanisms by which ion channel genes influence the progression of glioma are not fully understood. We identified KCNB1 as a novel ion gene, associated with malignant progression and favorable overall survival (OS) and progression-free survival (PFS) in glioma patients from three datasets (CGGA, GSE16011 and REMBRANDT). Moreover, we characterized a novel function of autophagy induction accompanied by increased apoptosis and reduced proliferation and invasion of glioma cells for KCNB1. KEGG pathway analysis andin vitrostudies suggested that the ERK pathway is involved in KCNB1-mediated regulation of autophagy, which was confirmed by inhibition of KCNB1-induced autophagy by using a selective ERK1/2 inhibitor (U0126) or siERK1/2.In vivostudies showed that KCNB1 induced autophagy while inhibiting tumor growth and increasing survival. Overall, our studies define KCNB1 as a novel prognostic factor for gliomas that exerts its tumor suppressive function through autophagy induction.