microRNA-34a is tumor suppressive in brain tumors and glioma stem cells.
microRNA-34a is tumor suppressive in brain tumors and glioma stem cells.
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DOI：
10.4161/cc.9.6.10987
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发表时间：
2010-03-15
期刊：
影响因子：
--
通讯作者：
Abounader R
中科院分区：
文献类型：
--
作者：
Guessous F;Zhang Y;Kofman A;Catania A;Li Y;Schiff D;Purow B;Abounader R
我们最近发现microRNA-34a(miR-34a)在人脑胶质瘤中表达下调，突变型p53胶质瘤的miR-34a水平低于野生型p53胶质瘤。我们发现miR-34a在胶质瘤和髓母细胞瘤细胞中的表达抑制了细胞的增殖、G1/S细胞周期进程、细胞存活、细胞迁移和细胞侵袭，但在人脑星形胶质细胞中的表达不影响细胞的存活和细胞周期。我们发现癌基因c-Met、Notch-1和Notch-2是miR-34a的直接靶点，它们被miR-34a转染所抑制。我们发现人脑胶质瘤标本中c-Met水平与miR-34a水平呈负相关。我们发现c-Met和Notch部分介导了miR-34a对细胞增殖和细胞死亡的抑制作用。我们还发现mir-34a的表达抑制了异种胶质瘤的体内生长。我们得出结论，miR-34a是一种潜在的脑肿瘤抑制因子，它通过靶向多个癌基因发挥作用。在这个额外的视角中，我们简要回顾和讨论这些发现的含义，并提供关于miR-34a在胶质瘤干细胞中的作用的新数据。新的数据显示，miR-34a的表达抑制了胶质瘤干细胞中的各种恶性终点。重要的是，他们还首次表明miR-34a的表达诱导胶质瘤干细胞分化。总之，这些数据表明miR-34a是一种肿瘤抑制因子和潜在的有效治疗剂，它通过靶向脑肿瘤的多条致癌途径和通过诱导癌症干细胞分化来发挥作用。
We recently found that microRNA-34a (miR-34a) is downregulated in human glioma tumors as compared to normal brain, and that miR-34a levels in mutant-p53 gliomas were lower than in wildtype-p53 tumors. We showed that miR-34a expression in glioma and medulloblastoma cells inhibits cell proliferation, G1/S cell cycle progression, cell survival, cell migration and cell invasion, but that miR-34a expression in human astrocytes does not affect cell survival and cell cycle. We uncovered the oncogenes c-Met, Notch-1 and Notch-2 as direct targets of miR-34a that are inhibited by miR-34a transfection. We found that c-Met levels in human glioma specimens inversely correlate with miR-34a levels. We showed that c-Met and Notch partially mediate the inhibitory effects of miR-34a on cell proliferation and cell death. We also found that mir-34a expression inhibits in vivo glioma xenograft growth. We concluded that miR-34a is a potential tumor suppressor in brain tumors that acts by targeting multiple oncogenes. In this extra view, we briefly review and discuss the implications of these findings and present new data on the effects of miR-34a in glioma stem cells. The new data show that miR-34a expression inhibits various malignancy endpoints in glioma stem cells. Importantly, they also show for the first time that miR-34a expression induces glioma stem cell differentiation. Altogether, the data suggest that miR-34a is a tumor suppressor and a potential potent therapeutic agent that acts by targeting multiple oncogenic pathways in brain tumors and by inducing the differentiation of cancer stem cells.
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DOI：
10.1146/annurev.pathol.4.110807.092222
发表时间：
2009
期刊：
Annual review of pathology
影响因子：
--
作者：
Lee YS;Dutta A
通讯作者：
Dutta A
影响因子：
4.7
作者：
Purow, Benjamin W.;Sundaresan, Tilak K.;Fine, Howard A.
通讯作者：
Fine, Howard A.
影响因子：
11.2
作者：
Purow, BW;Haque, RM;Fine, HA
通讯作者：
Fine, HA
影响因子：
64.8
作者：
He, Lin;He, Xingyue;Hannon, Gregory J.
通讯作者：
Hannon, Gregory J.
DOI：
10.1093/jnci/91.18.1548
发表时间：
1999-09-15
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Abounader, R;Ranganathan, S;Laterra, J
通讯作者：
Laterra, J