Differentially expressed miRNAs in Ewing sarcoma compared to mesenchymal stem cells: low miR-31 expression with effects on proliferation and invasion.
Differentially expressed miRNAs in Ewing sarcoma compared to mesenchymal stem cells: low miR-31 expression with effects on proliferation and invasion.
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DOI：
10.1371/journal.pone.0093067
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Bräuninger A
中科院分区：
文献类型：
--
作者：
Karnuth B;Dedy N;Spieker T;Lawlor ER;Gattenlöhner S;Ranft A;Dirksen U;Jürgens H;Bräuninger A
尤文肉瘤是儿童和年轻人第二常见的骨肿瘤，是一种侵袭性恶性肿瘤，具有很强的转移潜力。尤文肉瘤的特征是编码融合转录因子的易位，其中EWSR 1反式激活结构域与ETS家族DNA结合结构域融合。microRNA是基因表达的转录后调节因子，并且异常表达的microRNA已被鉴定为大多数癌症类型中的肿瘤抑制因子或致癌基因。为了鉴定尤文肉瘤中潜在的致癌和抑癌microRNA，我们测定并比较了来自6名健康供体的40例尤文肉瘤活检组织、6个尤文肉瘤细胞系和间充质干细胞（尤文肉瘤的假定细胞来源）中377种microRNA的表达。在鉴定的35种差异表达的microRNA中（倍数变化>4且q<0.05），19种在尤文肉瘤中表达较高，16种表达较低。在具有EWS-FLI或EWS-ERG易位的尤文肉瘤样品之间的比较中，具有不同的传播特征以及原发样品和转移样品，使用各种严格标准未检测到显著差异表达的microRNA。对于miR-31，与间充质干细胞相比具有最低表达的microRNA，进行功能分析以确定其作为尤文肉瘤中的肿瘤抑制剂的潜力。四种miR-31转染的尤文肉瘤细胞系中有两种显示出显著降低的增殖（19%和33%的减少），这是由于一种细胞系的凋亡增加和另一种细胞系的G1期长度增加。所有三种测试的miR-31转染的尤文肉瘤细胞系均显示出显著降低的侵袭性（降低56%至71%）。总之，我们鉴定了35种在尤文肉瘤中差异表达的microRNA，并证明了miR-31在离体测定中影响尤文肉瘤细胞系的增殖和侵袭。
Ewing sarcoma, the second most common bone tumor in children and young adults, is an aggressive malignancy with a strong potential to metastasize. Ewing sarcoma is characterised by translocations encoding fusion transcription factors with an EWSR1 transactivation domain fused to an ETS family DNA binding domain. microRNAs are post-transcriptional regulators of gene expression and aberrantly expressed microRNAs have been identified as tumor suppressors or oncogenes in most cancer types. To identify potential oncogenic and tumor suppressor microRNAs in Ewing sarcoma, we determined and compared the expression of 377 microRNAs in 40 Ewing sarcoma biopsies, 6 Ewing sarcoma cell lines and mesenchymal stem cells, the putative cellular origin of Ewing sarcoma, from 6 healthy donors. Of the 35 differentially expressed microRNAs identified (fold change >4 and q<0.05), 19 were higher and 16 lower expressed in Ewing sarcoma. In comparisons between Ewing sarcoma samples with EWS-FLI or EWS-ERG translocations, with differing dissemination characteristics and of primary samples and metastases no significantly differential expressed microRNAs were detected using various stringency criteria. For miR-31, the microRNA with lowest expression in comparison to mesenchymal stem cells, functional analyses were performed to determine its potential as a tumor suppressor in Ewing sarcoma. Two of four miR-31 transfected Ewing sarcoma cell lines showed a significantly reduced proliferation (19% and 33% reduction) due to increased apoptosis in one and increased length of G1-phase in the other cell line. All three tested miR-31 transfected Ewing sarcoma cell lines showed significantly reduced invasiveness (56% to 71% reduction). In summary, we identified 35 microRNAs differentially expressed in Ewing sarcoma and demonstrate that miR-31 affects proliferation and invasion of Ewing sarcoma cell lines in ex vivo assays.
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影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
影响因子：
6.2
作者：
Avigad, S;Cohen, IJ;Yaniv, I
通讯作者：
Yaniv, I
影响因子：
45.3
作者：
Paulussen, Michael;Craft, Alan W.;Juergens, Herbert
通讯作者：
Juergens, Herbert
影响因子：
11.2
作者：
Creighton CJ;Fountain MD;Yu Z;Nagaraja AK;Zhu H;Khan M;Olokpa E;Zariff A;Gunaratne PH;Matzuk MM;Anderson ML
通讯作者：
Anderson ML
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y