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Mol Cancer. 2010 Sep 2;9:229. doi: 10.1186/1476-4598-9-229.

MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma.

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1
Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China.

Abstract

BACKGROUND:

MiR-221 and miR-222 (miR-221/222) are frequently up-regulated in various types of human malignancy including glioblastoma. Recent studies have reported that miR-221/222 regulate cell growth and cell cycle progression by targeting p27 and p57. However the underlying mechanism involved in cell survival modulation of miR-221/222 remains elusive.

RESULTS:

Here we showed that miR-221/222 inhibited cell apoptosis by targeting pro-apoptotic gene PUMA in human glioma cells. Enforced expression of miR-22/222 induced cell survival whereas knockdown of miR-221/222 rendered cells to apoptosis. Further, miR-221/222 reduced PUMA protein levels by targeting PUMA-3'UTR. Introducing PUMA cDNA without 3'UTR abrogated miR-221/222-induced cell survival. Notably, knockdown of miR-221/222 induces PUMA expression and cell apoptosis and considerably decreases tumor growth in xenograft model. Finally, there was an inverse relationship between PUMA and miR-221/222 expression in glioma tissues.

CONCLUSION:

To our knowledge, these data indicate for the first time that miR-221/222 directly regulate apoptosis by targeting PUMA in glioblastoma and that miR-221/222 could be potential therapeutic targets for glioblastoma intervention.

PMID:
20813046
PMCID:
PMC2939570
DOI:
10.1186/1476-4598-9-229
[Indexed for MEDLINE]
Free PMC Article
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