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Regulation of fibroblast growth factor-2 by an endogenous antisense RNA and by argonaute-2

Leigh-Ann MacFarlane1, Ying Gu, Alan G Casson

  • 1Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.

Molecular Endocrinology (Baltimore, Md.)
|March 4, 2010
PubMed

Insights

Fibroblast growth factor-2 (FGF-2) and its antisense RNA (FGF-AS) mutually regulate each other in lung adenocarcinoma cells. FGF-AS targets FGF-2 mRNA, influencing tumor recurrence and survival.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • RNA Biology

Background:

  • Elevated fibroblast growth factor-2 (FGF-2) expression correlates with poor outcomes in esophageal cancer.
  • Coexpression of endogenous antisense (FGF-AS) RNA with FGF-2 is associated with reduced tumor recurrence and improved survival.

Purpose of the Study:

  • To investigate the regulatory role of endogenous FGF-AS in controlling FGF-2 expression within human lung adenocarcinoma cells (Seg-1).

Main Methods:

  • Utilized small interfering RNAs (siRNAs) to knock down FGF-2 and FGF-AS expression.
  • Employed a luciferase reporter system to analyze mRNA interactions.
  • Performed deletion mapping to identify specific RNA binding sites.
  • Assessed mRNA stability and protein expression levels.
  • Investigated the involvement of argonaute-2 (AGO-2) and micro-RNA pathways.

Main Results:

  • FGF-2 and FGF-AS were found to be colocalized in the cytoplasm and mutually regulate each other's expression and stability.
  • FGF-AS directly targets the 3'-untranslated region of FGF-2 mRNA.
  • Knockdown of FGF-AS led to decreased expression of AGO-2 and other RNA interference pathway components.
  • Knockdown of AGO-2 increased FGF-2 mRNA stability and protein levels, suggesting its role in FGF-2 regulation.

Conclusions:

  • Endogenous FGF-AS plays a critical role in regulating FGF-2 expression in lung adenocarcinoma through direct interaction with FGF-2 mRNA.
  • The FGF-2/FGF-AS axis and the AGO-2 protein are key components in the post-transcriptional regulation of FGF-2, impacting cancer progression.

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