Effect of BRAFV600E mutation on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model.
Effect of BRAFV600E mutation on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model.
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DOI：
10.1186/1476-4598-6-21
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发表时间：
2007-03-13
期刊：
影响因子：
37.3
通讯作者：
Sheils O
中科院分区：
文献类型：
--
作者：
Cahill S;Smyth P;Denning K;Flavin R;Li J;Potratz A;Guenther SM;Henfrey R;O'Leary JJ;Sheils O
microRNAs （miRNAs）是一组长度约为22个核苷酸的非编码单链rna，已被发现可控制细胞生长、分化和凋亡。它们负调控靶基因，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，这些基因被认为既是肿瘤抑制基因，也是致癌基因。最近，BRAF基因的点突变导致V600E替代被确定为甲状腺乳头状癌（PTC）中最常见的遗传改变，发生在29-69%的病例中。这种突变导致与肿瘤发生有关的MAPK异常激活。本研究的目的是通过microRNA分析确定BRAF致癌基因对PTC转录后调控的影响。具有BRAF突变的PTC细胞系与正常甲状腺细胞系之间具有独特的miRNA表达特征。15个mirna表达上调，23个mirna表达下调。这些上调/下调的mirna可能参与了PTC的发病机制。miRNA分析将有助于阐明疾病的发病机制和识别生物标志物和靶点。
microRNAs (miRNAs) are a group of non-coding single stranded RNAs measuring approximately 22 nucleotides in length that have been found to control cell growth, differentiation and apoptosis. They negatively regulate target genes and have recently been implicated in tumourigenesis. Furthermore, miRNA expression profiling correlates with various cancers, with these genes thought to act as both tumour suppressors and oncogenes. Recently, a point mutation in the BRAF gene leading to a V600E substitution has been identified as the most common genetic change in papillary thyroid carcinoma (PTC) occurring in 29–69% of cases. This mutation leads to aberrant MAPK activation that is implicated in tumourigenesis. The aim of this study was to identify the effect that BRAF oncogene has on post-transcriptional regulation in PTC by using microRNA analysis. A unique miRNA expression signature differentiated between PTC cell lines with BRAF mutations and a normal thyroid cell line. 15 miRNAs were found to be upregulated and 23 miRNAs were downregulated. Several of these up/down regulated miRNAs may be involved in PTC pathogenesis. miRNA profiling will assist in the elucidation of disease pathogenesis and identification biomarkers and targets.
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