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 p38 MAPK (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.

解偶联蛋白2（UCP2）是线粒体内膜阴离子载体，并且正在成为ROS产生的负调节剂。在各种肿瘤中都检测到过表达UCP2，但在胶质母细胞瘤中的作用仍不清楚。使用组织芯片和公共数据库的询问，我们探讨了UCP2的表达在神经胶质瘤，特别是在GBM中上调，并且UCP2的过表达与神经胶质瘤患者的不良预后相关。为了进一步揭示UCP2在神经胶质瘤中的作用，构建了慢病毒引起的UCP2沉默的细胞系（U251，U87MG和A172），以研究沉默的UCP2表达如何体外影响细胞功能以及体内致瘤性。进行了基于RNA-Seq的基因组和途径分析，以阐明UCP2作用的潜在机制。我们的研究结果表明，UCP2沉默的神经胶质瘤细胞在裸鼠中显示出抑制的迁移，侵袭性，克隆形成性，增殖，促进的细胞凋亡和较弱的致瘤性。转录组分析表明p38 MAPK（丝裂原激活的蛋白激酶）信号网络的UCP2依赖性调节，这已通过qRT-PCR和Western blot进一步证实。我们的研究为UCP2在神经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见解。