Effects of hnRNP A2/B1 Knockdown on Inhibition of Glioblastoma Cell Invasion, Growth and Survival
Effects of hnRNP A2/B1 Knockdown on Inhibition of Glioblastoma Cell Invasion, Growth and Survival
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DOI：
10.1007/s12035-014-9080-3
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发表时间：
2016-03-01
影响因子：
5.1
通讯作者：
Cheng, Yuan
中科院分区：
文献类型：
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作者：
Deng, Jinmu;Chen, Song;Cheng, Yuan
核内不均一核糖核蛋白A2/B1（hnRNPA 2/B1）在影响细胞内前信使RNA（pre-mRNA）的加工和mRNA的代谢与转运中起重要作用。越来越多的证据表明hnRNP A2/B1在人类多种肿瘤的发生、发展中起着重要作用。应用免疫组化方法检测40例正常脑组织和人脑胶质瘤组织中hnRNPA 2/B1蛋白的表达。采用RNA干扰（RNA interference，RNAi）技术敲低hnRNP A2/B1表达，分析hnRNP A2/B1在胶质母细胞瘤细胞存活、粘附、迁移、侵袭和替莫唑胺（temozolomide，TMZ）耐药中的作用。hnRNP A2/B1蛋白在胶质瘤组织标本中呈高表达，且与胶质瘤的分级有关。hnRNP A2/B1基因的敲除可降低胶质母细胞瘤细胞的存活率、粘附性、迁移性、侵袭性和对TMZ的耐药性，但可诱导胶质瘤U251和SHG 44细胞凋亡和活性氧（ROS）的产生。在分子水平上，hnRNPA 2/B1敲低降低了磷酸化STAT 3和MMP-2的表达。检测hnRNP A2/B1的表达可作为预测胶质瘤进展的生物标志物，敲低hnRNP A2/B1表达可作为临床控制胶质母细胞瘤的新策略。
Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) plays an important role in influence of pre-messenger RNA (pre-mRNA) processing and mRNA metabolism and transportation in cells. Increasing evidence indicates that hnRNP A2/B1 played an important role in development and progression of various human cancers. Forty cases of normal and human glioma tissue samples were analyzed using immunohistochemistry to reveal the expression of hnRNP A2/B1 protein in the samples. Then, knockdown of hnRNP A2/B1 expression induced by RNA interference (RNAi) method was used to analyze the role of hnRNP A2/B1 in glioblastoma cell viability, adhesion, migration, invasion, and chemoresistance for temozolomide (TMZ). The data showed that hnRNP A2/B1 protein was overexpressed in glioma tissue specimens and associated with advanced glioma grades. Knockdown of hnRNP A2/B1 could reduce glioblastoma cell viability, adhesion, migration, invasion, and chemoresistance for TMZ capacity, but induced tumor cells to apoptosis and reactive oxygen species (ROS) generation in glioma U251 and SHG44 cells. Molecularly, hnRNP A2/B1 knockdown reduced expression of phospho-STAT3 and MMP-2. Detection of hnRNP A2/B1 expression may be useful as a biomarker for prediction of glioma progression and knockdown of hnRNP A2/B1 expression as a novel strategy in future control of glioblastoma in clinic.