Lipoprotein lipase and phospholipid transfer protein overexpression in human glioma cells and their effect on cell growth, apoptosis, and migration
Lipoprotein lipase and phospholipid transfer protein overexpression in human glioma cells and their effect on cell growth, apoptosis, and migration
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人胶质瘤细胞中脂蛋白脂肪酶和磷脂转移蛋白的过度表达及其对细胞生长、凋亡和迁移的影响
DOI：
10.1093/abbs/gmw117
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发表时间：
2017-01-01
影响因子：
3.7
通讯作者：
Zheng, Jin
中科院分区：
文献类型：
--
作者：
Dong, Weijiang;Gong, Huilin;Zheng, Jin
胶质瘤是脑内常见的肿瘤之一。脂蛋白脂酶（LPL）和磷脂转运蛋白（PLTP）的表达水平可能影响胶质瘤的进展及其与临床和病理参数的关系。LPL或PLTP在胶质瘤中表达的临床意义尚未确定。本研究通过检测脑胶质瘤组织中LPL和PLTP水平，分析LPL和PLTP水平与脑胶质瘤恶性程度的关系，以期为脑胶质瘤的临床和基础研究提供新的思路。Ⅳ级胶质瘤中LPL和PLTP的mRNA和蛋白水平均显著高于低级别胶质瘤（P < 0.01）。免疫荧光双标显示LPL和PLTP水平与胶质瘤病理分级显著相关（P = 0.005）。LPL和PLTP水平随胶质瘤患者生存期的缩短而升高（P < 0.001）。在体外，LPL和PLTP的敲低导致细胞生长和迁移减少，但凋亡增加。此外，细胞周期相关的细胞周期蛋白和他们的合作伙伴被发现是下调，而细胞周期蛋白依赖性激酶抑制剂p16，p21，和Rb的上调。此外，LPL或PLTP的敲低导致促凋亡分子的上调和抗凋亡分子的下调。在U251细胞中去除LPL或PLTP导致上皮间质转化标志物和侵袭分子基质金属蛋白酶的下调。LPL和PLTP是新发现的胶质瘤相关蛋白，在胶质瘤的发生发展中起重要作用。
Glioma is one of the common tumors in brain. The expression level of lipoprotein lipase (LPL) or phospholipid transfer protein (PLTP) may influence glioma progression and its relationship with clinical and pathological parameters. The clinical significance of LPL or PLTP expression in glioma has not been established. In the present study, the LPL and PLTP levels in glioma tumors were investigated and the relationship between the LPL and PLTP level and the grade of malignant glioma was analyzed, with the aim to provide new ideas for the diagnosis and treatment of gliomas in clinical and basic research settings. LPL and PLTP mRNA and protein levels were significantly higher in Grade IV glioma than those in the lower grade tumors (P < 0.01). Double immunofluorescent staining showed that the levels of LPL and PLTP were significantly associated with the pathological grade of glioma (P = 0.005). The levels of LPL and PLTP were increased with the shortened survival of glioma patients (P < 0.001). Knockdown of LPL and PLTP led to decreased cell growth and migration but increased apoptosis in vitro. Additionally, cell cycle-related cyclins and their partners were found to be down-regulated while cyclin-dependent kinase inhibitors p16, p21, and Rb were up-regulated. Furthermore, knockdown of LPL or PLTP resulted in the up-regulation of pro-apoptotic molecules and the down-regulation of anti-apoptotic molecules. Ablation of LPL or PLTP in U251 cells resulted in the down-regulation of epithelial mesenchymal transition markers and invasion molecules matrix metalloproteinases. LPL and PLTP appear to be novel glioma-associated proteins and play a role in the progression of human glioma.