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

<p>Abstract</p> <p>Background</p> <p>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...

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Main Authors: 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
Format: Article
Language:English
Published: BMC 2010-09-01
Series:Molecular Cancer
Online Access:http://www.molecular-cancer.com/content/9/1/229
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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
author_facet 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
author_sort Zhang Chun-Zhi
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>
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spelling doaj.art-9189ba54beca48af8ae69c0c04b40c802022-12-21T19:08:32ZengBMCMolecular Cancer1476-45982010-09-019122910.1186/1476-4598-9-229MiR-221 and miR-222 target PUMA to induce cell survival in glioblastomaZhang Chun-ZhiZhang Jun-XiaZhang An-LingShi Zhen-DongHan LeiJia Zhi-FanYang Wei-DongWang Guang-XiuJiang TaoYou Yong-PingPu Pei-YuCheng Jin-QuanKang Chun-Sheng<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>http://www.molecular-cancer.com/content/9/1/229
spellingShingle 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
MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma
Molecular Cancer
title MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma
title_full MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma
title_fullStr MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma
title_full_unstemmed MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma
title_short MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma
title_sort mir 221 and mir 222 target puma to induce cell survival in glioblastoma
url http://www.molecular-cancer.com/content/9/1/229
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