The fibroblast growth factor-2 antisense gene inhibits nuclear accumulation of FGF-2 and delays cell cycle progression in C6 glioma cells.
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.
Baguma-Nibasheka
Mark
M
Department of Physiology and Biophysics, Dalhousie University, 5850 College Street, Halifax, Nova Scotia, Canada B3H 1X5.
Li
Audrey W
AW
Murphy
Paul R
PR
D000818:Animals; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D005910:Glioma / Q000473:pathology*; D021381:Protein Transport; D016372:RNA, Antisense / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D044967:Serum; D013347:Subcellular Fractions
C520403:NUDT6 protein, rat; D016372:RNA, Antisense; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D005346:Fibroblast Growth Factors