MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma.
MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma.
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miR-221 和 miR-222 靶向 PUMA 以诱导胶质母细胞瘤细胞存活。
DOI：
10.1186/1476-4598-9-229
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发表时间：
2010-09-02
期刊：
影响因子：
37.3
通讯作者：
Kang CS
中科院分区：
文献类型：
--
作者：
Zhang CZ;Zhang JX;Zhang AL;Shi ZD;Han L;Jia ZF;Yang WD;Wang GX;Jiang T;You YP;Pu PY;Cheng JQ;Kang CS
miR-221和miR-222（miR-221/222）在包括胶质母细胞瘤在内的各种类型的人类恶性肿瘤中频繁上调。最近的研究报道，miR-221/222通过靶向p27和p57调节细胞生长和细胞周期进程。然而，涉及miR-221/222的细胞存活调节的潜在机制仍然难以捉摸。在此，我们发现miR-221/222通过靶向人胶质瘤细胞中的促凋亡基因cDNAA来抑制细胞凋亡。miR-22/222的增强表达诱导细胞存活，而miR-221/222的敲低使细胞凋亡。此外，miR-221/222通过靶向CD 3A-3 'UTR降低CD 3A蛋白水平。引入不含3 'UTR的cDNA消除了miR-221/222诱导的细胞存活。值得注意的是，miR-221/222的敲低诱导了cDNAA表达和细胞凋亡，并显著降低了异种移植模型中的肿瘤生长。最后，在胶质瘤组织中，miR-221/222的表达与CD 45 A呈负相关。据我们所知，这些数据首次表明，miR-221/222通过靶向胶质母细胞瘤中的CRYSTA直接调节细胞凋亡，并且miR-221/222可能是胶质母细胞瘤干预的潜在治疗靶点。
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. 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. 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.
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