MicroRNA (miR) 125b regulates cell growth and invasion in pediatric low grade glioma.

MicroRNA (miR) 125b regulates cell growth and invasion in pediatric low grade glioma.
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DOI:
10.1038/s41598-018-30942-4
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发表时间:
2018-08-21
期刊:
影响因子:
4.6
通讯作者:
Rodriguez FJ
Rodriguez FJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yuan M;Da Silva ACAL;Arnold A;Okeke L;Ames H;Correa-Cerro LS;Vizcaino MA;Ho CY;Eberhart CG;Rodriguez FJ

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miR-125家族的成员在几种组织中强烈表达,特别是脑,但在包括成人和儿童胶质瘤在内的癌症中可能失调。在这项研究中,在Agilent平台中,与非肿瘤性脑相比,miR-125成员在毛细胞性星形细胞瘤(PA)中作为一个组下调。在Nanostring平台中,miR-125成员主要在多形性黄色星形细胞瘤和神经节细胞胶质瘤中下调。对于miR-125 b使用CISH,最高水平的表达存在于II级肿瘤中(11/33,33%的II级肿瘤具有3+表达,相比之下,3/70,4%的I级肿瘤)(p < 0.001)。当集中在两个组织学亚组与最大数量的样本,PA和弥漫性星形细胞瘤(DA),最高的表达水平出现在DA,与PA组相比(p = 0.01)。miR-125 b在儿童低级别胶质瘤(PLGG)衍生的细胞系(Res 186、Res 259和BT 66)中的过表达导致生长和侵袭减少以及凋亡。此外,BT 66中miR-125 b过表达导致衰老。这些发现表明,miR-125在PLGG中经常表达不足,过表达导致细胞生长减少和诱导凋亡,鉴于其作为PLGG新治疗策略的潜力,这些发现值得进一步研究。
Members of the miR-125 family are strongly expressed in several tissues, particularly brain, but may be dysregulated in cancer including adult and pediatric glioma. In this study, miR-125 members were downregulated in pilocytic astrocytoma (PA) as a group compared to non-neoplastic brain in the Agilent platform. In the Nanostring platform, miR-125 members were downregulated primarily in pleomorphic xanthoastrocytomas and gangliogliomas. Using CISH for miR-125b, highest levels of expression were present in grade II tumors (11/33, 33% grade II tumors with 3+ expression compared to 3/70, 4% grade I tumors) (p < 0.001). When focusing on the two histologic subgroups with the largest number of samples, PA and diffuse astrocytoma (DA), the highest expression levels were present in DA, in comparison with the PA group (p = 0.01). Overexpression of miR-125b in pediatric low grade glioma (PLGG) derived cell lines (Res186, Res259, and BT66) resulted in decreased growth and invasion, as well as apoptosis. Additionally, miR-125b overexpression in BT66 resulted in senescence. These findings suggest that miR-125 is frequently underexpressed in PLGG, and overexpression results in a decrease in cell growth and induction of apoptosis, findings that deserve further investigation given its potential as a novel therapeutic strategy for PLGG.
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