Baguma-Nibasheka Mark, Li Audrey W, Murphy Paul R
Department of Physiology and Biophysics, Dalhousie University, 5850 College Street, Halifax, Nova Scotia, Canada B3H 1X5.
Mol Cell Endocrinol. 2007 Mar 15;267(1-2):127-36. doi: 10.1016/j.mce.2007.01.008. Epub 2007 Jan 21.
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 G1 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.
成纤维细胞生长因子-2（FGF-2）是一种具有促生长和抗凋亡活性的强效肝素结合蛋白。位于相反DNA链上的GFG/NUDT6基因转录产生一种重叠反义RNA（FGF-AS），它参与FGF-2的转录后调控。C6胶质瘤细胞以细胞周期依赖性方式协同表达FGF-2和FGF-AS mRNA。细胞FGF-2免疫反应性也呈细胞周期依赖性，在S期有明显的核内积聚。FGF-AS RNA的稳定转染和过表达导致细胞总FGF-2受到抑制，且FGF-2亚型的核内积聚减少。血清刺激生长停滞的野生型细胞会引起FGF-2的快速核转位以及细胞周期重新进入。相比之下，FGF-AS转染细胞在核FGF-2染色恢复和S期重新进入方面均出现明显延迟。当细胞从阿非迪霉素诱导的G1期停滞中释放或受到热休克时，也观察到了类似结果。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内积聚，这与S期进程的明显延迟有关。结果提示，内源性FGF反义RNA可能在表达FGF-2的细胞中FGF-2依赖性细胞增殖的调控中发挥重要功能作用。
