Peroxisome proliferator-activated receptor δ (PPAR-δ), one of three PPAR subtypes, is a lipid-sensing nuclear receptor that has been implicated in multiple processes, including inflammation and cancer. To directly establish the role of PPAR-δ in colon cancer development and progression, we selected high-affinity RNA aptamers and expressed them in several colon cancer cell lines. Nuclear-expressed aptamers efficiently inhibited PPAR-δ-dependent transcription from a synthetic peroxisome proliferator response element-driven luciferase reporter. PPAR-δ-specific aptamers suppressed transcription from natural promoters of vascular endothelial cell growth factor-A and cyclooxygenase-2. Moreover, vascular endothelial cell growth factor-A and cyclooxygenase-2 mRNA levels were significantly reduced by the PPAR-δ-specific aptamers in colon cancer cells. Most significantly, HCT116 colon cancer cells with high-level expression of PPAR-δ-specific aptamers exhibited a striking loss of tumorigenic potential. Further study on these RNA aptamers could provide an opportunity to modulate PPAR-δ-mediated colon cancer development and progression. Taken together, our results establish an important role for PPAR-δ in transcription of tumorpromoting genes, which can be specifically modulated by high-affinity RNA intramers in colon cancer cells. The RNA intramers may be further developed as specific inhibitors for cancer therapeutic strategies. [Mol Cancer Ther 2009;8(9):2664-73]
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