In:
Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 8, No. 9 ( 2009-09-01), p. 2664-2673
Abstract:
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 tumor-promoting 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]
Type of Medium:
Online Resource
ISSN:
1535-7163
,
1538-8514
DOI:
10.1158/1535-7163.MCT-09-0214
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2009
detail.hit.zdb_id:
2062135-8
SSG:
12
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