NUPR1的下调通过ERK1/2、p38 MAPK和caspase-3抑制胶质母细胞瘤细胞的增殖

2016年12月，大连医科大学**附属医院神经外科;大连医科大学**附属医院介入治疗科(Department of Neurosurgery, First Affiliated Hospital of Dalian Medical University, 222 Zhong Shan Road, Dalian 116011, People’s Republic of China；Department of Interventional Therapy, First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China) Jun

Li老师研究团队在《JOURNAL OF NEUROSURGERY》上发表论文：

“Knockdown of NUPR1 inhibits the proliferation of glioblastoma cells via ERK1/2, p38 MAPK and caspase-3”

“NUPR1的下调通过ERK1/2、p38 MAPK和caspase-3抑制胶质母细胞瘤细胞的增殖”

Abstract：

Nuclear protein-1 (NUPR1), located on chromosome 16p11.2, is a stress response factor that plays an important role in the growth and migration of human malignant tumor cells. However, the role of NUPR1 in glioblastoma remains poorly understood. The expression level of NUPR1 was detected by quantitative real-time PCR and immunohistochemistry (IHC). Wound healing, MTT, cell counting and BrdU assays were used to analyze the migration and proliferation of glioblastoma cells after down-regulating NUPR1 expression using a lentiviral vector. FACS analysis and a signaling antibody array kit were used to detect the mechanism by which NUPR1 modulates cell cycle and apoptosis activities in glioblastoma cells. We confirmed that NUPR1 was up-regulated in glioblastoma tissues compared to NB tissues. Down-regulation of NUPR1 suppressed cell migration and proliferation, arrested the cell cycle in the G0/G1 phase and promoted apoptosis in U251 and U87 cells in vitro. Furthermore, the expression levels of phosphorylated ERK1/2, p38 MAPK and cleaved caspase-3 were decreased upon silencing NUPR1 expression in U251 and U87 cells. In summary, NUPR1 plays an important role in the growth and migration of human glioblastoma cells. Knockdown of NUPR1 suppressed glioblastoma cell growth by arresting the cell cycle and inducing cell apoptosis via decreases in the expression of ERK1/2, p38 MAPK and caspase-3.

摘要：

核蛋白-1 (Nuclear protein-1, NUPR1)位于染色体16p11.2上，是一种应激反应因子，在人类恶性肿瘤细胞的生长和迁移中起重要作用。然而，NUPR1在胶质母细胞瘤中的作用仍然知之甚少。采用实时荧光定量PCR和免疫组化(IHC)检测NUPR1的表达水平。采用慢病毒载体下调NUPR1表达后，采用伤口愈合、MTT、细胞计数和BrdU检测胶质母细胞瘤细胞的迁移和增殖情况。利用FACS分析和信号抗体阵列试剂盒检测NUPR1调控胶质母细胞瘤细胞周期和凋亡活性的机制。我们证实，与NB组织相比，NUPR1在胶质母细胞瘤组织中表达上调。下调NUPR1可抑制体外U251和U87细胞的迁移和增殖，使细胞周期停留在G0/G1期，促进细胞凋亡。此外，在U251和U87细胞中，沉默NUPR1表达后，磷酸化的ERK1/2、p38 MAPK和cleaved caspase-3的表达水平降低。综上所述，NUPR1在人胶质母细胞瘤细胞的生长和迁移中起着重要的作用。敲低NUPR1通过降低ERK1/2、p38 MAPK和caspase-3的表达，通过抑制细胞周期和诱导细胞凋亡来抑制胶质母细胞瘤细胞的生长。

该论文中，U87, U251, U373和A172人胶质瘤细胞系的体外培养是使用Ausbian特级胎牛血清完成的。欲了解或购买Ausbian特级胎牛血清可以联系北京缔一生物400-166-8600.