NUPR1的下調(diào)通過ERK1/2、p38 MAPK和caspase-3抑制膠質(zhì)母細(xì)胞瘤細(xì)胞的增殖

2016年12月，大連醫(yī)科大學(xué)**附屬醫(yī)院神經(jīng)外科;大連醫(yī)科大學(xué)**附屬醫(yī)院介入治療科(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老師研究團隊在《JOURNAL OF NEUROSURGERY》上發(fā)表論文：

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

“NUPR1的下調(diào)通過ERK1/2、p38 MAPK和caspase-3抑制膠質(zhì)母細(xì)胞瘤細(xì)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)位于染色體16p11.2上，是一種應(yīng)激反應(yīng)因子，在人類惡性腫瘤細(xì)胞的生長和遷移中起重要作用。然而，NUPR1在膠質(zhì)母細(xì)胞瘤中的作用仍然知之甚少。采用實時熒光定量PCR和免疫組化(IHC)檢測NUPR1的表達水平。采用慢病毒載體下調(diào)NUPR1表達后，采用傷口愈合、MTT、細(xì)胞計數(shù)和BrdU檢測膠質(zhì)母細(xì)胞瘤細(xì)胞的遷移和增殖情況。利用FACS分析和信號抗體陣列試劑盒檢測NUPR1調(diào)控膠質(zhì)母細(xì)胞瘤細(xì)胞周期和凋亡活性的機制。我們證實，與NB組織相比，NUPR1在膠質(zhì)母細(xì)胞瘤組織中表達上調(diào)。下調(diào)NUPR1可抑制體外U251和U87細(xì)胞的遷移和增殖，使細(xì)胞周期停留在G0/G1期，促進細(xì)胞凋亡。此外，在U251和U87細(xì)胞中，沉默NUPR1表達后，磷酸化的ERK1/2、p38 MAPK和cleaved caspase-3的表達水平降低。綜上所述，NUPR1在人膠質(zhì)母細(xì)胞瘤細(xì)胞的生長和遷移中起著重要的作用。敲低NUPR1通過降低ERK1/2、p38 MAPK和caspase-3的表達，通過抑制細(xì)胞周期和誘導(dǎo)細(xì)胞凋亡來抑制膠質(zhì)母細(xì)胞瘤細(xì)胞的生長。

該論文中，U87, U251, U373和A172人膠質(zhì)瘤細(xì)胞系的體外培養(yǎng)是使用Ausbian特級胎牛血清完成的。欲了解或購買Ausbian特級胎牛血清可以聯(lián)系北京締一生物400-166-8600.