Chen H-C, Chen G-H, Chen Y-H, Liao W-L, Liu C-Y, Chang K-P, Chang Y-S, Chen S-J
Genomic Core Laboratory, Molecular Medicine Research Center, Chang Gung University, Taiwan, Republic of China.
Br J Cancer. 2009 Mar 24;100(6):1002-11. doi: 10.1038/sj.bjc.6604948.
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.
微小RNA(miRNA)是一类长度约为20 - 23个核苷酸的小型非编码RNA分子,它们在转录后水平对蛋白质编码基因进行负调控。我们采用茎环实时定量PCR方法,对13例鼻咽癌(NPC)样本和9例癌旁正常组织中270种人类miRNA的表达水平进行了定量分析,并鉴定出35种在NPC样本中表达水平发生显著改变的miRNA。在NPC中上调的miRNA包括一些已知的致癌miRNA,如miR - 17 - 92簇和miR - 155。而肿瘤抑制性miRNA,如miR - 34家族、miR - 143和miR - 145,在NPC中显著下调。为了探究这些失调的miRNA在NPC发病机制中的作用,我们进行了一项计算分析,以预测22种显著下调的miRNA共同靶向的信号通路。下调的miRNA显著靶向了一些在癌症中特征明确的生物学信号通路。这些通路包括TGF - Wnt信号通路、G1 - S细胞周期进程、VEGF信号通路、凋亡和生存信号通路以及IP3信号通路。在NPC组织中,G1 - S进程和VEGF信号通路中几个预测靶基因的表达水平升高,且与下调的miRNA呈负相关。这些结果表明,这些下调的miRNA在NPC中协同调控了多个致癌信号通路。
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