miR-495 and miR-551a inhibit the migration and invasion of human gastric cancer cells by directly interacting with PRL - 3

The phosphatase of regenerating liver-3 (PRL-3) gene is associated with metastasis in gastric cancer, and is believed to play a causative role by promoting tumor cell motility, invasion, and metastasis, but little is known of the mechanisms involved. We previously reported that PRL-3 expression is s...

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Veröffentlicht in:Cancer letters 2012-10, Vol.323 (1), p.41-47
Hauptverfasser: Li, Zhengrong, Cao, Yi, Jie, Zhigang, Liu, Yi, Li, Yingliang, Li, Junhe, Zhu, Guoming, Liu, Zhengren, Tu, Yi, Peng, Gen, Lee, Dong-woo, Park, Sung-soo
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Sprache:eng
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Zusammenfassung:The phosphatase of regenerating liver-3 (PRL-3) gene is associated with metastasis in gastric cancer, and is believed to play a causative role by promoting tumor cell motility, invasion, and metastasis, but little is known of the mechanisms involved. We previously reported that PRL-3 expression is significantly higher in the tissues of primary gastric carcinomas with peritoneal metastasis. In the present study, we found that two microRNAs (miRNAs), miR-495 and miR-551a, predicted to target PRL-3, are downregulated in gastric carcinoma samples. The validation of this interaction between those two miRNAs and PRL-3 was confirmed by western blotting and quantitative real-time PCR (qPCR) in GC cell lines transfected with miR-495 and miR-551a mimics. Furthermore, the migration and invasion of GC cells were significantly inhibited by transfection with miR-495 or -551a mimics, and the mRNA and protein levels of PRL-3 were reduced in cells overexpressing miR-495 or -551a. Collectively, our findings suggest that miR-495 and miR-551a both act as tumor suppressors by targeting the PRL-3 oncogene and inhibiting gastric cancer cell migration and invasion. The findings of this study contribute to current understanding of the functions of miRNA mimics in GC gene therapy.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2012.03.029