Decreased Expression of MiRNA-204-5p Contributes to Glioma Progression and Promotes Glioma Cell Growth, Migration and Invasion.

Decreased Expression of MiRNA-204-5p Contributes to Glioma Progression and Promotes Glioma Cell Growth, Migration and Invasion.
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miRNA-204-5p 表达降低有助于神经胶质瘤进展并促进神经胶质瘤细胞生长、迁移和侵袭

DOI:
10.1371/journal.pone.0132399
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Liu L
Liu L
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Xia Z;Liu F;Zhang J;Liu L

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胶质瘤是成人最常见的恶性原发性脑肿瘤,表现出一系列异常的侵袭性表型。尽管越来越多的证据表明microRNA(miRNAs)的失调有助于肿瘤的发生和侵袭,但对miR-204- 5 p在人类胶质瘤中的作用知之甚少。在本研究中,通过qRT-PCR检测临床胶质瘤组织中miR-204- 5 p的表达。通过过表达或抑制miR-204 - 5 p来检查miR-204 - 5 p对胶质瘤细胞生长和转移的影响。我们发现miR-204- 5 p在临床胶质瘤组织中的表达水平较正常脑组织明显降低。此外,我们发现miR-204- 5 p的引入显著抑制胶质瘤细胞的生长、迁移和侵袭。此外,机制研究表明,RAB 22 A,RAS癌基因家族的成员,是胶质瘤中miR-204- 5 p的直接功能靶标。在体内,恢复胶质瘤细胞中的miR-204- 5 p表达抑制肿瘤发生并增加总体宿主存活。我们的研究结果表明,miR-204- 5 p是一种抑癌miRNA,过表达miR-204- 5 p是一种新的胶质瘤治疗策略。
Gliomas are the most common malignant primary brain tumors in adults and exhibit a spectrum of aberrantly aggressive phenotype. Although increasing evidence indicated that the deregulation of microRNAs (miRNAs) contributes to tumorigenesis and invasion, little is known about the roles of miR-204-5p in human gliomas. In the present study, the expression of miR-204-5p in clinical glioma tissues was measured by qRT-PCR. The effects of miR-204-5p on glioma cell growth and metastasis were examined by overexpressing or inhibiting miR-204-5p. We found that the expression level of miR-204-5p was significantly reduced in clinical glioma tissues compared with normal brain tissues. Moreover, we revealed that the introduction of miR-204-5p dramatically suppressed glioma cell growth, migration and invasion. Furthermore, mechanistic investigations revealed that RAB22A, a member of the RAS oncogene family, is a direct functional target of miR-204-5p in gliomas. In vivo, restoring miR-204-5p expression in glioma cells suppressed tumorigenesis and increased overall host survival. Our findings suggest that miR-204-5p is a cancer suppressor miRNA and overexpression of miR-204-5p is a novel glioma treatment strategy.
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