Abstract | BACKGROUND: METHODS:
miRNA microarray analysis using IFN-α-resistant clones of PLC/PRF/5 (PLC-Rs) and their parental cells (PLC-P) was conducted. Changes in the anti- cancer effects of IFN-α were studied after gain-of-function and loss-of-function of the candidate miRNA. RESULTS: miR-146a expression was significantly higher in PLC-Rs than in PLC-P. miR-146a decreased the sensitivity to IFN-α through the suppression of apoptosis. Further experiments showed that miR-146a-related resistance to IFN-α was mediated through SMAD4. CONCLUSIONS: The results indicated that miR-146a regulated the sensitivity of HCC cells to the cytotoxic effects of IFN-α through SMAD4, suggesting that this miRNA could be suitable for prediction of the clinical response and potential therapeutic target in HCC patients on IFN-based therapy.
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Authors | Akira Tomokuni, Hidetoshi Eguchi, Yoshito Tomimaru, Hiroshi Wada, Koichi Kawamoto, Shogo Kobayashi, Shigeru Marubashi, Masahiro Tanemura, Hiroaki Nagano, Masaki Mori, Yuichiro Doki |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 414
Issue 4
Pg. 675-80
(Nov 04 2011)
ISSN: 1090-2104 [Electronic] United States |
PMID | 21982769
(Publication Type: Journal Article)
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Copyright | Copyright © 2011 Elsevier Inc. All rights reserved. |
Chemical References |
- Interferon-alpha
- MIRN146 microRNA, human
- MicroRNAs
- SMAD4 protein, human
- Smad4 Protein
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Topics |
- Apoptosis
(drug effects)
- Carcinoma, Hepatocellular
(drug therapy)
- Cell Line, Tumor
- Drug Resistance, Neoplasm
(genetics)
- Humans
- Interferon-alpha
(therapeutic use)
- Liver Neoplasms
(drug therapy)
- MicroRNAs
(genetics)
- Smad4 Protein
(metabolism)
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