Interaction of hsa-miR-381 and glioma suppressor LRRC4 is involved in glioma growth
Interaction of hsa-miR-381 and glioma suppressor LRRC4 is involved in glioma growth
复制标题
hsa-miR-381 和神经胶质瘤抑制因子 LRRC4 的相互作用参与神经胶质瘤生长
DOI：
10.1016/j.brainres.2011.03.034
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发表时间：
2011-05-16
期刊：
影响因子：
2.9
通讯作者：
Li, Guiyuan
中科院分区：
文献类型：
--
作者：
Tang, Hailin;Liu, Xiaoping;Li, Guiyuan
LRRC 4不仅是脑特异性基因，而且已被鉴定为胶质瘤的肿瘤抑制基因。LRRC 4启动子甲基化常参与胶质瘤的失活。最近研究表明，miRNA介导的基因调控在肿瘤（包括胶质瘤）的多种生物学过程中发挥重要作用。在这项研究中，我们证明了一种小的调节性microRNA，hsa-miR-381，一种“oncomir”，在胶质瘤进展中具有重要作用，并且LRRC 4是hsa-miR-381的靶点。hsa-miR-381通过调节LRRC 4增加胶质瘤细胞的体外和体内增殖，并且这种作用与MEK/ERK和AKT信号传导抑制降低有关。相反，LRRC 4作为胶质瘤抑制因子，抑制hsa-miR-381的内源性表达，并降低细胞增殖和肿瘤生长。hsa-miR-381与LRRC 4的相互作用参与了胶质瘤的发病机制。此外，hsa-miR-381在血液中的稳定表达提供了一种新的、有前景的诊断生物标志物，抗hsa-miR-381的“Hisomir”可能是胶质瘤治疗的理想靶点。(C)2011 Elsevier B. V.保留所有权利。
LRRC4 is not only a brain-specific gene, but it has also been identified as a tumor suppressor gene for glioma. Promoter methylation of LRRC4 is frequently involved in the inactivation in glioma. MiRNA-mediated gene regulation has recently been demonstrated to play an important role in multiple biological processes related to cancer, including glioma. In this study, we demonstrated that a small regulatory microRNA, hsa-miR-381, an "oncomir", had a major role in glioma progression and that LRRC4 was a target of hsa-miR-381. By regulating LRRC4, hsa-miR-381 increased the in vitro and in vivo proliferation of glioma cells, and this action was associated with decreased inhibition of MEK/ERK and AKT signaling. Conversely, LRRC4, as a glioma suppressor, inhibited the endogenous expression of hsa-miR-381 and decreased cell proliferation and tumor growth. The interaction of hsa-miR-381 and LRRC4 is involved in the pathogenesis of glioma. In addition, the stable expression of hsa-miR-381 in blood provides a novel and promising diagnostic biomarker, and anti-hsa-miR-381 "antagomir" may be an ideal target for glioma therapy. (C) 2011 Elsevier B.V. All rights reserved.