Effect of ret/PTC 1 rearrangement on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model.

Effect of ret/PTC 1 rearrangement on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model.
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DOI:
10.1186/1476-4598-5-70
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发表时间:
2006-12-11
期刊:
影响因子:
37.3
通讯作者:
Sheils O
Sheils O
中科院分区:
医学1区
文献类型:
--
作者:
Cahill S;Smyth P;Finn SP;Denning K;Flavin R;O'Regan EM;Li J;Potratz A;Guenther SM;Henfrey R;O'Leary JJ;Sheils O

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microRNA(miRNAs)是一组长度约为22 nt的非编码单链RNA,已发现其控制细胞生长、分化和凋亡。miRNAs负调控其靶基因,最近被认为与肿瘤发生有关。此外,miRNA表达谱与各种癌症相关,这些基因被认为是肿瘤抑制基因和癌基因。ret/PTC 1是一种具有组成性激酶活性的癌基因,与甲状腺乳头状癌(PTC)的发生有关。这种重排导致异常的MAPK活化,其与PTC肿瘤发生有关。本研究的目的是通过DNA微阵列和microRNA分析来鉴定ret/PTC 1在PTC中的转录和转录后调控作用。DNA微阵列分析揭示了一组基因之间的差异表达正常甲状腺细胞系和那些窝藏ret/PTC 1重排。此外,一个独特的miRNA表达签名区分PTC细胞系与ret/PTC 1和正常甲状腺细胞系。与正常甲状腺细胞相比,21个miRNAs在这些细胞系中显示显著的过表达,14个miRNAs显示低表达。这些上调/下调的miRNAs中的一些可能参与PTC的发病机制。
microRNAs (miRNAs) are a group of non-coding single stranded RNAs measuring approximately 22 nt in length that have been found to control cell growth, differentiation and apoptosis. miRNAs negatively regulate their target genes and recently have been implicated in tumourigenesis. Furthermore, miRNA expression profiling correlates with various cancers, with these genes thought to act as both tumour suppressors and oncogenes. ret/PTC 1 is an oncogene with constitutive kinase activity implicated in the development of papillary thyroid carcinoma (PTC). This rearrangement leads to aberrant MAPK activation that is implicated in PTC tumourigenesis. The aim of this study was to identify the effect that ret/PTC 1 has on transcription and post-transcriptional regulation in PTC by using DNA microarray and microRNA analysis. DNA microarray analysis revealed a group of genes differentially expressed between normal thyroid cell lines and those harbouring a ret/PTC 1 rearrangement. Furthermore, a unique miRNA expression signature differentiated between PTC cell lines with ret/PTC 1 and a normal thyroid cell line. 21 miRNAs showed significant overexpression and 14 miRNAs showed underexpression in these cell lines when compared to normal thyroid. Several of these up/down regulated miRNAs may be involved in PTC pathogenesis.
DOI: 10.1038/nature03702
发表时间: 2005-06-09
期刊: NATURE
影响因子: 64.8
作者:
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通讯作者: Golub, TR
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影响因子: 11.1
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期刊: LEUKEMIA RESEARCH
影响因子: 2.7
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期刊: CELL
影响因子: 64.5
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