The fibroblast growth factor-2 antisense gene inhibits nuclear accumulation of FGF-2 and delays cell cycle progression in C6 glioma cells
The fibroblast growth factor-2 antisense gene inhibits nuclear accumulation of FGF-2 and delays cell cycle progression in C6 glioma cells
复制标题
DOI：
10.1016/j.mce.2007.01.008
复制
发表时间：
2007-03-15
影响因子：
4.1
通讯作者：
Murphy, Paul R.
中科院分区：
文献类型：
--
作者：
Baguma-Nibasheka, Mark;Li, Audrey W.;Murphy, Paul R.
成纤维细胞生长因子-2（FGF-2）是一种有效的肝素结合蛋白，具有促生长和抗凋亡活性。相反DNA链上GFG/NUDT 6基因的转录产生了一个重叠的反义RNA（FGF-AS），参与FGF-2的转录后调节。C6胶质瘤细胞以细胞周期依赖的方式协调表达FGF-2和FGF-AS mRNA。细胞FGF-2免疫反应性也是细胞周期依赖性的，在S期具有显著的核积聚。FGF-AS RNA的稳定转染和过表达导致总细胞FGF-2的抑制和FGF-2同种型的核积累的减少。血清刺激生长停滞的野生型细胞引起FGF-2的快速核转位，并重新进入细胞周期。相比之下，FGF-AS转染子在细胞核FGF-2染色和S期再进入的恢复方面显示出显著延迟。当细胞从aphidicolin诱导的G1期阻滞释放或受到热休克时，观察到类似的结果。这些发现表明，FGF-AS RNA抑制FGF-2的表达和细胞周期依赖性核积累，这与S期进展的显著延迟有关。结果表明，内源性FGF反义RNA可能在FGF-2表达细胞中FGF-2依赖性细胞增殖的调节中发挥重要的功能作用。(c)2007爱思唯尔爱尔兰有限公司保留所有权利。
Fibroblast growth factor-2 (FGF-2) is a potent heparin-binding protein with growth-promoting and anti-apoptotic activity. Transcription of the GFG/NUDT6 gene on the opposite DNA strand generates an overlapping antisense RNA (FGF-AS) implicated in the post-transcriptional regulation of FGF-2. C6 glioma cells coordinately express FGF-2 and FGF-AS mRNA in a cell cycle-dependent manner. Cellular FGF-2 immunoreactivity was also cell cycle-dependent, with marked nuclear accumulation during S-phase. Stable transfection and overexpression of the FGF-AS RNA resulted in suppression of total cellular FGF-2, and a reduction in nuclear accumulation of FGF-2 isoforms. Serum stimulation of growth-arrested wild-type cells evoked a rapid nuclear translocation of FGF-2, and cell cycle re-entry. FGF-AS transfectants, in contrast, showed a significant delay in recovery of both nuclear FGF-2 staining and S-phase re-entry. Similar results were observed when cells were released from aphidicolin-induced G 1 arrest or subjected to heat shock. These findings indicate that FGF-AS RNA inhibits expression and cell cycle-dependent nuclear accumulation of FGF-2, and this is associated with a marked delay in S-phase progression. The results suggest that the endogenous FGF antisense RNA may play a significant functional role in the regulation of FGF-2 dependent cell proliferation in FGF-2 expressing cells. (c) 2007 Elsevier Ireland Ltd. All rights reserved.