MicroRNA deregulation and pathway alterations in nasopharyngeal carcinoma.

MicroRNA deregulation and pathway alterations in nasopharyngeal carcinoma.
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DOI:
10.1038/sj.bjc.6604948
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发表时间:
2009-03-24
影响因子:
8.8
通讯作者:
Chen, S-J
Chen, S-J
中科院分区:
医学1区
文献类型:
--
作者:
Chen, H-C;Chen, G-H;Chen, Y-H;Liao, W-L;Liu, C-Y;Chang, K-P;Chang, Y-S;Chen, S-J

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MicroRNAs(MiRNAs)是一个长度约为20-23个核苷酸的非编码小RNA分子家族,在转录后水平对蛋白质编码基因进行负调控。采用茎环实时定量聚合酶链式反应方法,定量检测了270个人miRNAs在13例鼻咽癌组织和9例癌旁正常组织中的表达水平,发现了35个在鼻咽癌组织中表达水平显著改变的miRNAs。已知的几个致癌miRNAs,包括miR-17-92簇和miR-155,都是在鼻咽癌中上调的miRNAs。抑制肿瘤的miRNAs,包括miR-34家族、miR-143和miR-145,在鼻咽癌中表达显著下调。为了探讨这些异常的miRNAs在鼻咽癌发病机制中的作用,进行了一项计算分析,以预测22个显著下调的miRNAs共同靶向的通路。一些在癌症中被很好地描述的生物途径被下调的miRNAs显著地作为靶点。这些通路包括转化生长因子-Wnt通路、细胞周期G1-S通路、血管内皮生长因子信号通路、细胞凋亡和存活通路以及IP3信号通路。在鼻咽癌组织中,G1-S进展和血管内皮细胞生长因子信号通路中几个预测的靶基因的表达水平升高,并与下调的miRNAs呈负相关。这些结果表明,这些下调的miRNAs协同调节鼻咽癌中的几条致癌途径。
MicroRNAs (miRNAs) are a family of small non-coding RNA molecules of about 20–23 nucleotides in length, which negatively regulate protein-coding genes at post-transcriptional level. Using a stem-loop real-time-PCR method, we quantified the expression levels of 270 human miRNAs in 13 nasopharyngeal carcinoma (NPC) samples and 9 adjacent normal tissues, and identified 35 miRNAs whose expression levels were significantly altered in NPC samples. Several known oncogenic miRNAs, including miR-17-92 cluster and miR-155, are among the miRNAs upregulated in NPC. Tumour suppressive miRNAs, including miR-34 family, miR-143, and miR-145, are significantly downregulated in NPC. To explore the roles of these dysregulated miRNAs in the pathogenesis of NPC, a computational analysis was performed to predict the pathways collectively targeted by the 22 significantly downregulated miRNAs. Several biological pathways that are well characterised in cancer are significantly targeted by the downregulated miRNAs. These pathways include TGF-Wnt pathways, G1-S cell cycle progression, VEGF signalling pathway, apoptosis and survival pathways, and IP3 signalling pathways. Expression levels of several predicted target genes in G1-S progression and VEGF signalling pathways were elevated in NPC tissues and showed inverse correlation with the down-modulated miRNAs. These results indicate that these downregulated miRNAs coordinately regulate several oncogenic pathways in NPC.
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