UCP2 silencing in glioblastoma reduces cell proliferation and invasiveness by inhibiting p38MAPK pathway
UCP2 silencing in glioblastoma reduces cell proliferation and invasiveness by inhibiting p38MAPK pathway
复制标题
胶质母细胞瘤中 UCP2 沉默通过抑制 p38MAPK 通路减少细胞增殖和侵袭
DOI：
10.1016/j.yexcr.2020.112110
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发表时间：
2020
影响因子：
3.7
通讯作者：
Dongxiao Zhuang
中科院分区：
文献类型：
--
作者：
Shuai Wu;Chen Luo;N.U. Farrukh Hameed;Ye Wang;Dongxiao Zhuang
解偶联蛋白-2(UCP2)是一种线粒体内膜阴离子载体，是ROS产生的负性调节因子。UCP2在多种肿瘤中均有过表达，但其在胶质母细胞瘤中的作用尚不清楚。利用组织芯片和公共数据库查询，我们发现UCP2在胶质瘤中表达上调，尤其是在GBM中，UCP2的过度表达与胶质瘤患者的预后不良有关。为了进一步揭示UCP2在胶质瘤中的作用，构建了慢病毒介导的UCP2沉默细胞系(U251、U87 MG和A172)，以研究UCP2沉默表达在体外对细胞功能和体内致瘤性的影响。通过基于RNA-Seq的基因组和通路分析来阐明UCP2的潜在作用机制。我们的结果显示，UCP2沉默的胶质瘤细胞在体外表现出抑制迁移、侵袭、克隆形成、增殖，促进细胞凋亡，以及在裸鼠体内较弱的致瘤性。转录组分析表明，UCP2依赖于p38áMAPK(丝裂原活化蛋白激酶)信号网络的调节，qRT-PCR和Western印迹进一步证实了这一点。我们的研究为UCP2在胶质瘤中的生物学意义及其在治疗和诊断中的潜在应用提供了新的视角。
Uncoupling protein-2 (UCP2) is a mitochondrial inner membrane anion carrier and is emerging as a negative regulator of ROS production. Overexpression of UCP2 has been detected in various tumors, but its role in glioblastoma remains unclear. Using tissue microarrays and interrogations of public databases, we explored that the expression of UCP2 is upregulated in glioma, especially in GBM, and overexpression of UCP2 correlates with poor prognosis in glioma patients. To further reveal the role of UCP2 in glioma, UCP2-slienced cell lines (U251, U87MG and A172) by lentivirus were constructed to study how silenced UCP2 expression affects cellular functions in vitro, and tumorigenicity in vivo. RNA-Seq based genome and pathway analysis were performed to elucidate the underlying mechanisms of action of UCP2. Our results revealed that UCP2 silenced glioma cells show inhibited migration, invasiveness, clonogenicity, proliferation, promoted cell apoptosis in vitro, and weaker tumorigenicity in nude mice. Transcriptome analysis suggested a UCP2-dependent regulation of p38áMAPK (Mitogen-activated protein kinase) signaling networks, which was further validated by qRT-PCR and Western blot. Our research provides a new insight into the biological significance of UCP2 in glioma and its potential application in treatment and diagnosis.