MiRNA-329 targeting E2F1 inhibits cell proliferation in glioma cells.
MiRNA-329 targeting E2F1 inhibits cell proliferation in glioma cells.
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靶向 E2F1 的 miRNA-329 抑制神经胶质瘤细胞的细胞增殖
DOI：
10.1186/1479-5876-11-172
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发表时间：
2013-07-17
影响因子：
7.4
通讯作者：
Xu R
中科院分区：
文献类型：
--
作者：
Xiao B;Tan L;He B;Liu Z;Xu R
microRNA是近年来出现的肿瘤的重要调控因子，位于14q32.31的miR-329是胶质瘤中下调的miRNAs之一，但miR-329在决定胶质瘤恶性表型中的功能和分子机制尚不清楚。本研究旨在探讨miR-329在人脑胶质瘤细胞系LN 18和T98 G生物学行为中的作用及其分子机制。通过定量RT-PCR分析9例GBM患者的miR-329表达。将miR-329前体转染入LN 18和T98 G细胞，建立miR-329过表达模型，采用MTT法、贴壁生长能力测定法、克隆形成实验、溴脱氧尿苷标记法和免疫荧光法研究miR-329过表达对LN 18和T98 G细胞增殖的影响。流式细胞仪检测miR-329对细胞周期的影响。通过荧光素酶测定确定miR-329的靶标。Western blot检测miR-329对Akt通路的调控作用。E2 F1被鉴定为miR-329的靶点。过表达miR-329可阻断LN 18和T98 G细胞系的G1/S转变，显着抑制细胞增殖和集落形成能力。miR-329可显著降低细胞内Akt磷酸化水平和cyclin D1表达，上调p21表达，通过抑制E2 F1介导的Akt通路抑制细胞生长。miR-329可能通过调节E2 F1介导的Akt通路抑制人脑胶质瘤细胞的增殖。
MicroRNAs have recently emerged as key regulators of cancers, miR-329 located on 14q32.31 is one of down-regulated miRNAs in glioma, but the function and molecular mechanisms of miR-329 in determining the malignant phenotype of human glioma are elusive. This study therefore was conducted to investigate the role of miR-329 in biological behaviors of human glioma LN18 and T98G cell lines and its molecular mechanisms. Nine patients with GBM were analyzed for the expression of miR-329 by quantitative RT–PCR. MiR-329 overexpression was established by transfecting miR-329 precursor into LN18 and T98G cells, and its effects on cell proliferation were studied using MTT assay, anchorage-independent growth ability assay, colony formation assays, Bromodeoxyuridine labeling and immunofluorescence. The effects of miR-329 on cell cycle were studied by flow cytometry. The target of miR-329 was determined by luciferase assays. The regulation of miR-329 on Akt pathway was determined by western blot. The E2F1 was identified as the target of miR-329. Overexpression of miR-329 blocked G1/S transition in LN18 and T98G cell lines, dramatically suppressed cell proliferation and the ability of colony formation. MiR-329 significantly decreased the phosphorylation levels of intracellular kinases Akt and expression of cyclin D1, but the expression of p21 was upregulated, cell growth was suppressed by inhibiting E2F1-mediated Akt pathway. MiR-329 may inhibit cell proliferation in human glioma cells through regulating E2F1-mediated suppression of Akt pathway.
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影响因子：
10.5
作者：
LaBaer, J;Garrett, MD;Harlow, E
通讯作者：
Harlow, E
影响因子：
3.7
作者：
Real S;Meo-Evoli N;Espada L;Tauler A
通讯作者：
Tauler A
影响因子：
8
作者：
Ernst, A.;Campos, B.;Radlwimmer, B.
通讯作者：
Radlwimmer, B.
影响因子：
64.8
作者：
O'Donnell, KA;Wentzel, EA;Mendell, JT
通讯作者：
Mendell, JT
影响因子：
4.8
作者：
Gera, JF;Mellinghoff, IK;Lichtenstein, AK
通讯作者：
Lichtenstein, AK