RNA G-Quadruplexes in Kirsten Ras (KRAS) Oncogene as Targets for Small Molecules Inhibiting Translation
Тип публикации: Journal Article
Дата публикации: 2017-12-01
scimago Q1
wos Q1
БС1
SJR: 1.801
CiteScore: 11.5
Impact factor: 6.8
ISSN: 00222623, 15204804
PubMed ID:
29140695
Drug Discovery
Molecular Medicine
Краткое описание
The human KRAS transcript contains a G-rich 5'-UTR sequence (77% GC) harboring several G4 motifs capable to form stable RNA G-quadruplex (RG4) structures that can serve as targets for small molecules. A biotin-streptavidin pull-down assay showed that 4,11-bis(2-aminoethylamino)anthra[2,3-b]furan-5,10-dione (2a) binds to RG4s in the KRAS transcript under low-abundance cellular conditions. Dual-luciferase assays demonstrated that 2a and its analogue 4,11-bis(2-aminoethylamino)anthra[2,3-b]thiophene-5,10-dione (2b) repress translation in a dose-dependent manner. The effect of the G4-ligands on Panc-1 cancer cells has also been examined. Both 2a and 2b efficiently penetrate the cells, suppressing protein p21KRAS to <10% of the control. The KRAS down-regulation induces apoptosis together with a dramatic reduction of cell growth and colony formation. In summary, we report a strategy to suppress the KRAS oncogene in pancreatic cancer cells by means of small molecules binding to RG4s in the 5'-UTR of mRNA.
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Miglietta G. et al. RNA G-Quadruplexes in Kirsten Ras (KRAS) Oncogene as Targets for Small Molecules Inhibiting Translation // Journal of Medicinal Chemistry. 2017. Vol. 60. No. 23. pp. 9448-9461.
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Miglietta G., Cogoi S., Marinello J., Capranico G., Tikhomirov A. S., Shchekotikhin A., Xodo L. RNA G-Quadruplexes in Kirsten Ras (KRAS) Oncogene as Targets for Small Molecules Inhibiting Translation // Journal of Medicinal Chemistry. 2017. Vol. 60. No. 23. pp. 9448-9461.
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TY - JOUR
DO - 10.1021/acs.jmedchem.7b00622
UR - https://doi.org/10.1021/acs.jmedchem.7b00622
TI - RNA G-Quadruplexes in Kirsten Ras (KRAS) Oncogene as Targets for Small Molecules Inhibiting Translation
T2 - Journal of Medicinal Chemistry
AU - Miglietta, Giulia
AU - Cogoi, Susanna
AU - Marinello, Jessica
AU - Capranico, Giovanni
AU - Tikhomirov, Alexander S
AU - Shchekotikhin, Andrey
AU - Xodo, Luigi
PY - 2017
DA - 2017/12/01
PB - American Chemical Society (ACS)
SP - 9448-9461
IS - 23
VL - 60
PMID - 29140695
SN - 0022-2623
SN - 1520-4804
ER -
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@article{2017_Miglietta,
author = {Giulia Miglietta and Susanna Cogoi and Jessica Marinello and Giovanni Capranico and Alexander S Tikhomirov and Andrey Shchekotikhin and Luigi Xodo},
title = {RNA G-Quadruplexes in Kirsten Ras (KRAS) Oncogene as Targets for Small Molecules Inhibiting Translation},
journal = {Journal of Medicinal Chemistry},
year = {2017},
volume = {60},
publisher = {American Chemical Society (ACS)},
month = {dec},
url = {https://doi.org/10.1021/acs.jmedchem.7b00622},
number = {23},
pages = {9448--9461},
doi = {10.1021/acs.jmedchem.7b00622}
}
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MLA
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Miglietta, Giulia, et al. “RNA G-Quadruplexes in Kirsten Ras (KRAS) Oncogene as Targets for Small Molecules Inhibiting Translation.” Journal of Medicinal Chemistry, vol. 60, no. 23, Dec. 2017, pp. 9448-9461. https://doi.org/10.1021/acs.jmedchem.7b00622.
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