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Differentially Expressed miRNAs in Hepatocellular Carcinoma Target Genes in the Genetic Information Processing and Metabolism Pathways

机译:肝细胞癌靶基因中的差异表达miRNA在遗传信息加工和代谢途径中的作用

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摘要

To date, studies of the roles of microRNAs (miRNAs) in hepatocellular carcinoma (HCC) have either focused on specific individual miRNAs and a small number of suspected targets or simply reported a list of differentially expressed miRNAs based on expression profiling. Here, we seek a more in-depth understanding of the roles of miRNAs and their targets in HCC by integrating the miRNA and messenger RNA (mRNA) expression profiles of tumorous and adjacent non-tumorous liver tissues of 100 HCC patients. We assessed the levels of 829 mature miRNAs, of which 32 were significantly differentially expressed. Statistical analysis indicates that six of these miRNAs regulate a significant proportion of their in silico predicted target mRNAs. Three of these miRNAs (miR-26a, miR-122, and miR-130a) were down-regulated in HCC, and their up-regulated gene targets are primarily associated with aberrant cell proliferation that involves DNA replication, transcription and nucleotide metabolism. The other three miRNAs (miR-21, miR-93, and miR-221) were up-regulated in HCC, and their down-regulated gene targets are primarily involved in metabolism and immune system processes. We further found evidence for a coordinated miRNA-induced regulation of important cellular processes, a finding to be considered when designing therapeutic applications based on miRNAs.
机译:迄今为止,对微小RNA(miRNA)在肝细胞癌(HCC)中的作用的研究要么集中于特定的单个miRNA和少数可疑靶标,要么只是基于表达谱分析报道了一系列差异表达的miRNA。在这里,我们通过整合100例HCC患者肿瘤和邻近非肿瘤肝组织的miRNA和信使RNA(mRNA)表达谱,寻求对miRNA及其靶标在HCC中的作用的更深入了解。我们评估了829个成熟miRNA的水平,其中32个显着差异表达。统计分析表明,这些miRNA中有6个调节其计算机预测的目标mRNA的显着比例。这些miRNA中的三个(miR-26a,miR-122和miR-130a)在HCC中被下调,其上调的基因靶标主要与异常细胞增殖有关,涉及DNA复制,转录和核苷酸代谢。其他三个miRNA(miR-21,miR-93和miR-221)在HCC中被上调,其下调的基因靶标主要参与代谢和免疫系统过程。我们进一步发现了协调一致的miRNA诱导的重要细胞过程调控的证据,这一发现在设计基于miRNA的治疗应用时应予以考虑。

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