miR-221/222 overexpession in human glioblastoma increases invasiveness by targeting the protein phosphate PTPμ.
miR-221/222 overexpession in human glioblastoma increases invasiveness by targeting the protein phosphate PTPμ.
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DOI：
10.1038/onc.2011.280
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发表时间：
2012-02-16
期刊：
影响因子：
8
通讯作者：
Condorelli, G.
中科院分区：
文献类型：
--
作者：
Quintavalle, C.;Garofalo, M.;Zanca, C.;Romano, G.;Iaboni, M.;De Caro, M. del Basso;Martinez-Montero, J. C.;Incoronato, M.;Nuovo, G.;Croce, C. M.;Condorelli, G.
胶质母细胞瘤是成人中最常见的脑肿瘤，也是人类癌症中最致命的形式。尽管治疗方法有所改进，但患者的生存率仍然很低。为了鉴定参与胶质瘤发生的microRNA（miRs），我们利用miRarray技术检测了胶质瘤LN-18、LN-229和U87 MG细胞与非胶质瘤T98 G细胞中miRs的差异表达。在不同的miR中，我们将注意力集中在miR-221和-222上。我们证明了在蛋白酪氨酸磷酸酶μ（PTPμ）的3′非翻译区存在这两个miR的结合位点。以前的研究表明PTPμ抑制细胞迁移，并在胶质母细胞瘤中下调。值得注意的是，我们发现miR-221和-222过表达诱导PTPμ的下调，通过Western blot和实时PCR分析。此外，miR-222和-221诱导胶质瘤细胞在软琼脂中的细胞迁移和生长增加。有趣的是，PTPμ基因的重新表达能够逆转miR-222和-221对细胞迁移的影响。此外，我们发现miR-221和-222和PTPμ在人类神经胶质瘤癌症样本中呈负相关。总之，我们的研究结果表明，miR-221和-222调节胶质瘤的肿瘤发生至少部分通过控制PTPμ蛋白的表达。
Glioblastoma is the most frequent brain tumor in adults and is the most lethal form of human cancer. Despite the improvements in treatments, survival of patients remains poor. In order to identify microRNAs (miRs) involved in glioma tumorigenesis, we evaluated, by a miRarray, differential expression of miRs in the tumorigenic glioma LN-18, LN-229 and U87MG cells compared with the non-tumorigenic T98G cells. Among different miRs we focused our attention on miR-221 and -222. We demonstrated the presence of a binding site for these two miRs in the 3′ untranslated region of the protein tyrosine phosphatase μ (PTPμ). Previous studies indicated that PTPμ suppresses cell migration and is downregulated in glioblastoma. Significantly, we found that miR-221 and -222 over-expression induced a downregulation of PTPμ as analyzed by both western blot and real-time PCR. Furthermore, miR-222 and -221 induced an increase in cell migration and growth in soft agar in glioma cells. Interestingly, the re-expression of PTPμ gene was able to revert the miR-222 and -221 effects on cell migration. Furthermore, we found an inverse correlation between miR-221 and -222 and PTPμ in human glioma cancer samples. In conclusion, our results suggest that miR-221 and -222 regulate glioma tumorigenesis at least in part through the control of PTPμ protein expression.
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影响因子：
12.7
作者：
DERIDDER, LI;LAERUM, OD;BIGNER, DD
通讯作者：
BIGNER, DD
影响因子：
50.3
作者：
Garofalo M;Di Leva G;Romano G;Nuovo G;Suh SS;Ngankeu A;Taccioli C;Pichiorri F;Alder H;Secchiero P;Gasparini P;Gonelli A;Costinean S;Acunzo M;Condorelli G;Croce CM
通讯作者：
Croce CM
影响因子：
11.2
作者：
Kefas, Benjamin;Godlewski, Jakub;Purow, Benjamin
通讯作者：
Purow, Benjamin
DOI：
10.1073/pnas.0403293101
发表时间：
2004-06-29
影响因子：
11.1
作者：
Liu, CG;Calin, GA;Croce, CM
通讯作者：
Croce, CM
影响因子：
3.9
作者：
Conti, Alfredo;Aguennouz, M'Hammed;Tomasello, Francesco
通讯作者：
Tomasello, Francesco