miR-422a Inhibits Glioma Proliferation and Invasion by Targeting IGF1 and IGF1R.

miR-422a Inhibits Glioma Proliferation and Invasion by Targeting IGF1 and IGF1R.
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miR-422a 通过靶向 IGF1 和 IGF1R 抑制胶质瘤增殖和侵袭

DOI:
10.3727/096504016x14732772150389
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发表时间:
2017-01-26
期刊:
影响因子:
3.1
通讯作者:
Lin Z
Lin Z
中科院分区:
医学2区
文献类型:
--
作者:
Wang H;Tang C;Na M;Ma W;Jiang Z;Gu Y;Ma G;Ge H;Shen H;Lin Z

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脑胶质瘤是一种常见的恶性脑肿瘤,具有侵袭性转移能力。最近的证据表明,非编码RNA,包括microRNA,在神经胶质瘤发展的病理生理学中具有重要的功能。本研究旨在探讨miR-422 a在人脑胶质瘤中的生物学功能。我们发现miR-422 a在胶质瘤组织中表达下调。我们还证实了miR-422 a在胶质瘤细胞中的表达显著抑制了细胞增殖、迁移和侵袭。此外,我们确定了胰岛素样生长因子1(IGF 1)和IGF 1受体(IGF 1 R)作为胶质瘤细胞中miR-422 a的抑制靶点。我们建立了miR-422 a的表达水平与IGF 1/IGF 1 R的表达水平和胶质瘤患者的临床参数呈负相关。IGFR抑制剂AG 1024完全阻断了miR-442 a对胶质瘤细胞增殖和侵袭的活性,进一步证实了miR-422 a通过IGF 1和IGF 1 R发挥作用。
Glioma is a common type of malignant brain tumor characterized by aggressive metastasis capability. Recent evidence has suggested that noncoding RNAs, including microRNAs, have important functions in the pathophysiology of glioma development. In this study, we investigated the biological function of miR-422a in human glioma. We found that miR-422a was downregulated in glioma tissues. We also demonstrated that expression of miR-422a in glioma cells markedly suppressed cell proliferation, migration, and invasion. In addition, we identified insulin-like growth factor 1 (IGF1) and IGF1 receptor (IGF1R) as inhibitory targets of miR-422a in glioma cells. We established that the expression levels of miR-422a were negatively correlated with the expression levels of IGF1/IGF1R and the clinical parameters in glioma patients. An IGFR inhibitor, AG1024, completely blocked the activity of miR-442a on glioma cell proliferation and invasion, which further confirmed that miR-422a functions through IGF1 and IGF1R.