MicroRNA-326 functions as a tumor suppressor in glioma by targeting the Nin one binding protein (NOB1).
MicroRNA-326 functions as a tumor suppressor in glioma by targeting the Nin one binding protein (NOB1).
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MicroRNA-326 通过靶向 Nin one 结合蛋白 (NOB1) 作为神经胶质瘤中的肿瘤抑制因子。
DOI：
10.1371/journal.pone.0068469
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Zhou J;Xu T;Yan Y;Qin R;Wang H;Zhang X;Huang Y;Wang Y;Lu Y;Fu D;Chen J
恶性胶质瘤是成人中最常见的原发性脑肿瘤类型，其特征在于肿瘤快速生长和肿瘤细胞浸润整个脑。26 S蛋白酶体活性的改变与恶性胶质瘤细胞有关，尽管具体的缺陷尚未确定。近年来发现microRNA-326（miR-326）在胶质母细胞瘤和乳腺癌中发挥重要作用，但其分子机制尚不清楚。在本研究中，人Nin one结合蛋白（NOB 1）被鉴定为miR-326的直接靶点，并且是人脑胶质瘤中的潜在癌基因。与NOB 1沉默类似，miR-326在人脑胶质瘤细胞系（A172和U373）中的过表达导致细胞周期停滞在G1期，延迟细胞增殖并增强凋亡。miR-326抑制软琼脂中的集落形成，并降低异种移植肿瘤模型的生长，表明miR-326和NOB 1是体外和体内肿瘤发生所必需的。此外，这些过程被证明涉及MAPK途径。通过Affyellow阵列分析检测人脑胶质瘤样品中NOB 1的过表达，并且与低级别胶质瘤和正常脑组织相比，NOB 1 mRNA和蛋白水平在高级别胶质瘤中显示出增加。此外，高水平的NOB 1与胶质瘤患者的不良预后相关。综上所述，这些结果表明，miR-326和NOB 1可能在胶质瘤的发展中发挥重要作用。
Malignant glioma is the most common type of primary brain tumor in adults, characterized by rapid tumor growth and infiltration of tumor cells throughout the brain. Alterations in the activity of the 26S proteasome have been associated with malignant glioma cells, although the specific defects have not been identified. Recently, microRNA-326 (miR-326) was shown to play an important role in glioblastoma and breast cancer, but the underlying molecular mechanisms remain unclear. In the present study, the human Nin one binding protein (NOB1) was identified as a direct target of miR-326 and a potential oncogene in human glioma. Similar to NOB1 silencing by shRNA, overexpression of miR-326 in human glioma cell lines (A172 and U373) caused cell cycle arrest at the G1 phase, delayed cell proliferation and enhanced apoptosis. MiR-326 inhibited colony formation in soft agar and decreased growth of a xenograft tumor model, suggesting that miR-326 and NOB1 are required for tumorigenesis in vitro and in vivo. Furthermore, these processes were shown to involve the MAPK pathway. NOB1 overexpression in human glioma samples was detected by Affymetrix array analysis, and NOB1 mRNA and protein levels were shown to be increased in high-grade glioma compared to low-grade glioma and normal brain tissue. Furthermore, high levels of NOB1 were associated with unfavorable prognosis of glioma patients. Taken together, these results indicate that miR-326 and NOB1 may play an important role in the development of glioma.
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影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
DOI：
10.3322/caac.20069
发表时间：
2010-05
期刊：
CA: a cancer journal for clinicians
影响因子：
--
作者：
Van Meir EG;Hadjipanayis CG;Norden AD;Shu HK;Wen PY;Olson JJ
通讯作者：
Olson JJ
影响因子：
2.5
作者：
Thatcher, Elizabeth J.;Flynt, Alex S.;Patton, James G.
通讯作者：
Patton, James G.
DOI：
10.1523/jneurosci.4966-09.2009
发表时间：
2009-12-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kefas B;Comeau L;Floyd DH;Seleverstov O;Godlewski J;Schmittgen T;Jiang J;diPierro CG;Li Y;Chiocca EA;Lee J;Fine H;Abounader R;Lawler S;Purow B
通讯作者：
Purow B
影响因子：
3.5
作者：
Tone, Y;Tanahashi, N;Toh-e, A
通讯作者：
Toh-e, A