MiR-503 regulates cisplatin resistance of human gastric cancer cell lines by targeting IGF1R and BCL2 / 中华医学杂志(英文版)
Chinese Medical Journal
;
(24): 2357-2362, 2014.
Artículo
en Inglés
| WPRIM
| ID: wpr-241668
ABSTRACT
<p><b>BACKGROUND</b>Studies have shown that the drug resistance of gastric cancer cells can be modulated by abnormal expression of microRNAs (miRNAs). We investigated the role of miR-503 in the development of cisplatin resistance in human gastric cancer cell lines.</p><p><b>METHODS</b>MiR-503 expression was measured by quantitative real-time PCR. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) and clonogenic assays were used to examine changes in cell viability and the drug resistance phenotype of cancer cells associated with upregulation or downregulation of the miRNA. A dual-luciferase activity assay was used to verify target genes of miR-503. Immunohistochemistry, Western blotting analysis, and a flow cytometric apoptosis assay were used to elucidate the mechanism by which miR-503 modulates drug resistance in cancer cells.</p><p><b>RESULTS</b>MiR-503 was significantly downregulated in gastric cancer tissues and several gastric cancer cell lines. Additionally, downregulation of miR-503 in the cisplatin (DDP)-resistant gastric cancer cell line SGC7901/DDP was concurrent with the upregulation of insulin-like growth factor-1 receptor (IGF1R) and B-cell lymphoma 2 (BCL2) expression compared with the parental SGC7901 cell line. An in vitro drug sensitivity assay showed that overexpression of miR-503 sensitized SGC7901/DDP cells to cisplatin. The luciferase activity of reporters driven by IGF1R and BCL2 3'-untranslated regions in SGC7901/DDP cells suggested that IGF1R and BCL2 were both direct target genes of miR-503. Enforced miR-503 expression in SGC7901/DDP cells reduced expression of the target proteins, inhibited proliferation, and sensitized the cells to DDP-induced apoptosis.</p><p><b>CONCLUSION</b>Our findings suggest that hsa-miR-503 modulates cisplatin resistance of human gastric cancer cells at least in part by targeting IGF1R and BCL2.</p>
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Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Farmacología
/
Neoplasias Gástricas
/
Inmunohistoquímica
/
Cisplatino
/
Apoptosis
/
Proteínas Proto-Oncogénicas c-bcl-2
/
MicroARNs
/
Línea Celular Tumoral
/
Proliferación Celular
/
Reacción en Cadena en Tiempo Real de la Polimerasa
Límite:
Humanos
Idioma:
Inglés
Revista:
Chinese Medical Journal
Año:
2014
Tipo del documento:
Artículo
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