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

2010; BioMed Central; Volume: 9; Issue: 1 Linguagem: Inglês

10.1186/1476-4598-9-229

1476-4598

Chun-zhi Zhang, Junxia Zhang, Anling Zhang, Zhendong Shi, Lei Han, Zhifan Jia, Weidong Yang, Guangxiu Wang, Tao Jiang, Yongping You, Peiyu Pu, Cheng Jinquan, Chunsheng Kang,

RNA Research and Splicing

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.