Division of Minimally Invasive Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung, 40705, Taiwan, ROC.
Department of Physical Therapy, Hung Kuang University, No. 160, Sec. 3 Taichung-Kang Rd., Taichung 407, Taichung, 43302, Taiwan, ROC.
J Neurooncol. 2018 Oct;140(1):37-47. doi: 10.1007/s11060-018-2928-z. Epub 2018 Jun 16.
A previous study confirmed that a novel splicing variant of large vascular endothelial growth factor (L-VEGF) termed L-VEGF144, a nucleolus protein, is found in glioblastoma cells and specimens, but the actual biological function and clinical significance of L-VEGF144 remain unclear.
In this study, we analyzed the expression of L-VEGF144 in 68 glioblastoma multiforme specimens using reverse transcriptase-polymerase chain reaction analysis.
The results showed that the high expression of L-VEGF144 was associated with a poor prognosis in the bevacizumab plus concurrent chemoradiotherapy with temozolomide treatment. In addition, we constructed a series truncated and mutant form of L-VEGF144 to confirm that exon 6a of L-VEGF144 is able to engage in the nuclear importation and found that 8 lysines within exon 6a play a critical role in the nucleolus aggregation of L-VEGF144. Also, the transfection of the L-VEGF144 increased the number of nucleoli. Furthermore, the recombinant protein Flag-L-VEGF144 and commercial VEGF protein have similar growth stimulatory activities in terms of inducing glioblastoma cell proliferation in vitro.
Taken together, these results indicated that the expression of L-VEGF144 could potentially serve as an independent indicator of poor prognosis in bevacizumab treatment.
先前的一项研究证实，一种名为 L-VEGF144 的新型剪接变体大血管内皮生长因子（L-VEGF），作为核仁蛋白，存在于神经胶质瘤细胞和标本中，但 L-VEGF144 的实际生物学功能和临床意义仍不清楚。
在这项研究中，我们使用逆转录聚合酶链反应分析分析了 68 例多形性胶质母细胞瘤标本中 L-VEGF144 的表达。
结果表明，L-VEGF144 的高表达与贝伐单抗联合替莫唑胺同期放化疗治疗的不良预后相关。此外，我们构建了一系列截短和突变形式的 L-VEGF144，以证实 L-VEGF144 的外显子 6a 能够参与核输入，并发现外显子 6a 内的 8 个赖氨酸在 L-VEGF144 的核仁聚集中起着关键作用。此外，L-VEGF144 的转染增加了核仁的数量。此外，重组蛋白 Flag-L-VEGF144 和商业 VEGF 蛋白在体外诱导神经胶质瘤细胞增殖方面具有相似的生长刺激活性。
综上所述，这些结果表明，L-VEGF144 的表达可能可作为贝伐单抗治疗不良预后的独立指标。
