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抑制信号转导和转录激活因子3(STAT3)可减少星形细胞瘤细胞的侵袭,而STAT3的组成性激活预示着人类星形细胞瘤的预后不良。

Inhibition of STAT3 reduces astrocytoma cell invasion and constitutive activation of STAT3 predicts poor prognosis in human astrocytoma.

作者信息

Liang Qinchuan, Ma Chenkai, Zhao Yang, Gao Guodong, Ma Jie

机构信息

Department of Pediatric Neurosurgery, Xin-Hua Hospital, Shanghai JiaoTong University, School of Medicine, Shanghai, People's Republic of China ; Department of Neurosurgery, Tang-Du Hospital, Institution for Functional Neurosurgery of P.L.A., Fourth Military Medical University, Xi'an, Shannxi Province, People's Republic of China.

Department of Pediatric Neurosurgery, Xin-Hua Hospital, Shanghai JiaoTong University, School of Medicine, Shanghai, People's Republic of China.

出版信息

PLoS One. 2013 Dec 30;8(12):e84723. doi: 10.1371/journal.pone.0084723. eCollection 2013.

DOI:10.1371/journal.pone.0084723
PMID:24386409
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3875539/
Abstract

Astrocytoma cells characteristically possess high invasion potentials. Recent studies have revealed that knockdown of signal transducers and activators of transcription 3 (STAT3) expression by RNAi induces apoptosis in astrocytoma cell. Nevertheless, the distinct roles of STAT3 in astrocytoma's invasion and recurrence have not been elucidated. In this study, we silenced STAT3 using Small interfering RNAs in two human glioblastoma multiforme (GBM) cell lines (U251 and U87), and investigated the effect on GBM cell adhesion and invasion. Our results demonstrate that disruption of STAT3 inhibits GBM cell's adhesion and invasion. Knockdown of STAT3 significantly increased E-cadherin but decreased N-cadherin, vascular endothelial growth factor, matrix metalloproteinase 2 and matrix metalloproteinase 9. Additionally, expression of pSTAT3(Tyr705) correlates with astrocytoma WHO classification, Karnofsky performance status scale score, tumor recurrence and survival. Furthermore, pSTAT3(Tyr705) is a significant prognostic factor in astrocytoma. In conclusion, STAT3 may affect astrocytoma invasion, expression of pSTAT3(Tyr705) is a significant prognostic factor in tumor recurrence and overall survival in astrocytoma patients. Therefore, STAT3 may provide a potential target for molecular therapy in human astrocytoma, and pSTAT3(Tyr705)could be an important biomarker for astrocytoma prognosis.

摘要

星形细胞瘤细胞通常具有较高的侵袭潜能。最近的研究表明,通过RNA干扰敲低信号转导和转录激活因子3(STAT3)的表达可诱导星形细胞瘤细胞凋亡。然而,STAT3在星形细胞瘤侵袭和复发中的独特作用尚未阐明。在本研究中,我们使用小干扰RNA在两个人类多形性胶质母细胞瘤(GBM)细胞系(U251和U87)中使STAT3沉默,并研究其对GBM细胞黏附和侵袭的影响。我们的结果表明,STAT3的破坏会抑制GBM细胞的黏附和侵袭。敲低STAT3可显著增加E-钙黏蛋白,但降低N-钙黏蛋白、血管内皮生长因子、基质金属蛋白酶2和基质金属蛋白酶9。此外,pSTAT3(Tyr705)的表达与星形细胞瘤WHO分级、卡诺夫斯基功能状态量表评分、肿瘤复发和生存相关。此外,pSTAT3(Tyr705)是星形细胞瘤的一个重要预后因素。总之,STAT3可能影响星形细胞瘤的侵袭,pSTAT3(Tyr705)的表达是星形细胞瘤患者肿瘤复发和总生存的一个重要预后因素。因此,STAT3可能为人类星形细胞瘤的分子治疗提供一个潜在靶点,而pSTAT3(Tyr705)可能是星形细胞瘤预后的一个重要生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cfd/3875539/d0195b895833/pone.0084723.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cfd/3875539/657088e631b2/pone.0084723.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cfd/3875539/f28b7af5c431/pone.0084723.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cfd/3875539/403dc84d3aaa/pone.0084723.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cfd/3875539/d0195b895833/pone.0084723.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cfd/3875539/657088e631b2/pone.0084723.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cfd/3875539/f28b7af5c431/pone.0084723.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cfd/3875539/403dc84d3aaa/pone.0084723.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cfd/3875539/d0195b895833/pone.0084723.g004.jpg

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