Modulation of transcription by the peroxisome proliferator-activated receptor delta--binding RNA aptamer in colon cancer cells.
Peroxisome proliferator-activated receptor delta (PPAR-delta), 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-delta 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-delta-dependent transcription from a synthetic peroxisome proliferator response element-driven luciferase reporter. PPAR-delta-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-delta-specific aptamers in colon cancer cells. Most significantly, HCT116 colon cancer cells with high-level expression of PPAR-delta-specific aptamers exhibited a striking loss of tumorigenic potential. Further study on these RNA aptamers could provide an opportunity to modulate PPAR-delta-mediated colon cancer development and progression. Taken together, our results establish an important role for PPAR-delta 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.
Kwak
Hoyun
H
Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University, Yongin-si, Gyeonggi-do 448-701, Republic of Korea.
Hwang
Injoo
I
Kim
Jee Ho
JH
Kim
Mee Young
MY
Yang
Ji Sun
JS
Jeong
Sunjoo
S
D052157:Aptamers, Nucleotide; D001483:Base Sequence; D049109:Cell Proliferation; D003001:Cloning, Molecular; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics; D017931:DNA Primers; D045325:HCT116 Cells; D006801:Humans; D047494:PPAR delta / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D051176:beta Catenin / Q000502:physiology
D052157:Aptamers, Nucleotide; D017931:DNA Primers; D047494:PPAR delta; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin; D051546:Cyclooxygenase 2