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


CONCLUSIONS
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.
Zhang
Chun-Zhi
CZ
Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China.
Zhang
Jun-Xia
JX
Zhang
An-Ling
AL
Shi
Zhen-Dong
ZD
Han
Lei
L
Jia
Zhi-Fan
ZF
Yang
Wei-Dong
WD
Wang
Guang-Xiu
GX
Jiang
Tao
T
You
Yong-Ping
YP
Pu
Pei-Yu
PY
Cheng
Jin-Quan
JQ
Kang
Chun-Sheng
CS
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D005260:Female; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D041681:NIH 3T3 Cells; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D051017:Apoptosis Regulatory Proteins; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C438378:BBC3 protein, human; C525709:MIR221, human; C546122:MIRN221 microRNA, mouse; C525710:MIR222, human; C546123:MIRN222 microRNA, mouse
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