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

Author:

Zhang Chun-Zhi,Zhang Jun-Xia,Zhang An-Ling,Shi Zhen-Dong,Han Lei,Jia Zhi-Fan,Yang Wei-Dong,Wang Guang-Xiu,Jiang Tao,You Yong-Ping,Pu Pei-Yu,Cheng Jin-Quan,Kang Chun-Sheng

Abstract

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.

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Oncology,Molecular Medicine

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