MiR-124-5p inhibits the growth of high-grade gliomas through posttranscriptional regulation of LAMB1
MiR-124-5p inhibits the growth of high-grade gliomas through posttranscriptional regulation of LAMB1
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MiR-124-5p 通过 LAMB1 的转录后调节抑制高级别胶质瘤的生长
DOI：
10.1093/neuonc/not300
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发表时间：
2014-05-01
期刊：
影响因子：
15.9
通讯作者：
Zhang, Shizhong
中科院分区：
文献类型：
--
作者：
Chen, Qiang;Lu, Guohui;Zhang, Shizhong
多形性胶质母细胞瘤（GBM）是人类脑肿瘤中最具侵袭性的形式。先前显示，高水平的层粘连蛋白-8表达是肿瘤复发和患者存活的预测因子。因此，重要的是要阐明层粘连蛋白-8表达的调节机制，并确定这是如何有助于胶质瘤的进展。本研究通过定量PCR和Western blotting检测LAMB 1和miR-124- 5 p在胶质瘤细胞系（U87和U251）和GBM组织中的表达水平，探讨LAMB 1在胶质瘤细胞系和GBM小鼠模型中的调控机制。通过评估恢复的miR-124 - 5 p表达对细胞增殖、集落形成以及肿瘤生长和血管生成的影响来研究miR-124 - 5 p对LAMB 1的潜在调节。LAMB 1表达上调与miR-124- 5 p表达下调高度相关。miR-124- 5 p抑制LAMB 1蛋白表达。miR-124- 5 p表达的恢复通过抑制血管生成抑制胶质瘤的生长，在LAMB 1敲除后也观察到这种作用，这一发现表明miR-124- 5 p具有肿瘤抑制剂的功能，可作为胶质瘤诊断的分子标志物和GBM治疗的潜在治疗靶点。
Glioblastoma multiforme (GBM) is the most aggressive form of human brain tumor. It was previously shown that high levels of laminin-8 expression were a predictor of tumor recurrence and patient survival. It is thus important to elucidate the mechanism by which laminin-8 expression is regulated and determine how this contributes to glioma progression. This study investigated the mechanism of regulation of LAMB1, which encodes the 1 chain of laminin-8, in glioma cells lines and in a mouse model of GBM.The expression levels of LAMB1 and miR-124-5p were examined in glioma cell lines (U87 and U251) and GBM tissue samples by quantitative PCR and Western blotting. The potential regulation of LAMB1 by miR-124-5p was investigated by assessing the effects of restored miR-124-5p expression on cell proliferation, colony formation, and tumor growth and angiogenesis. The effects of inhibiting LAMB1 on tumor growth and angiogenesis were also assessed.The upregulation of LAMB1 expression was highly correlated with the downregulation of miR-124-5p. LAMB1 protein expression was suppressed by miR-124-5p. The restoration of miR-124-5p expression suppressed glioma growth by inhibiting angiogenesis, effects that were also observed upon LAMB1 knockdown.The findings indicate that miR-124-5p functions as a tumor suppressor and could serve as a molecular marker for glioma diagnosis and as a potential therapeutic target in GBM treatment.