Dysregulated miR-671-5p / CDR1-AS / CDR1 / VSNL1 axis is involved in glioblastoma multiforme.
Dysregulated miR-671-5p / CDR1-AS / CDR1 / VSNL1 axis is involved in glioblastoma multiforme.
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DOI：
10.18632/oncotarget.6621
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发表时间：
2016-01-26
期刊：
影响因子：
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通讯作者：
Purrello M
中科院分区：
文献类型：
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作者：
Barbagallo D;Condorelli A;Ragusa M;Salito L;Sammito M;Banelli B;Caltabiano R;Barbagallo G;Zappalà A;Battaglia R;Cirnigliaro M;Lanzafame S;Vasquez E;Parenti R;Cicirata F;Di Pietro C;Romani M;Purrello M
MiR-671-5p由定位于7q36.1的基因编码，该区域在人类多形性胶质母细胞瘤（GBM）中扩增，这是最恶性的脑癌。为了研究miR-671-5p的表达是否在GBM中改变，我们分析了45名GBM患者和5个GBM细胞系的活检。我们的数据显示miR-671-5p在活组织检查和细胞系中显著过表达。通过利用特异性miRNA模拟物和抑制剂，我们证明miR-671-5p过表达显著增加GBM细胞的迁移和在较小程度上的增殖率。通过硅和体外结合的方法，我们确定了CDR1- as， CDR1， VSNL1是GBM中下游miR-671-5p的靶点。这些基因的表达在GBM活检组织和细胞系中均显著降低，并与miR-671-5p负相关。根据我们的数据，我们提出miR-671-5p / CDR1- as / CDR1 / VSNL1轴在GBM细胞中发生功能改变，并参与其生物病理学特征的改变。
MiR-671-5p is encoded by a gene localized at 7q36.1, a region amplified in human glioblastoma multiforme (GBM), the most malignant brain cancer. To investigate whether expression of miR-671-5p were altered in GBM, we analyzed biopsies from a cohort of forty-five GBM patients and from five GBM cell lines. Our data show significant overexpression of miR-671-5p in both biopsies and cell lines. By exploiting specific miRNA mimics and inhibitors, we demonstrated that miR-671-5p overexpression significantly increases migration and to a less extent proliferation rates of GBM cells. Through a combined in silico and in vitro approach, we identified CDR1-AS, CDR1, VSNL1 as downstream miR-671-5p targets in GBM. Expression of these genes significantly decreased both in GBM biopsies and cell lines and negatively correlated with that of miR-671-5p. Based on our data, we propose that the axis miR-671-5p / CDR1-AS / CDR1 / VSNL1 is functionally altered in GBM cells and is involved in the modification of their biopathological profile.