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首页> 外文期刊>Molecular medicine reports >A pleiotropic effect of the single clustered hepatic metastamiRs miR-96-5p and miR-182-5p on insulin-like growth factor II, insulin-like growth factor-1 receptor and insulin-like growth factor-binding protein-3 in hepatocellular carcinoma
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A pleiotropic effect of the single clustered hepatic metastamiRs miR-96-5p and miR-182-5p on insulin-like growth factor II, insulin-like growth factor-1 receptor and insulin-like growth factor-binding protein-3 in hepatocellular carcinoma

机译：单簇肝转移瘤miR-96-5p和miR-182-5p对肝细胞癌中胰岛素样生长因子II，胰岛素样生长因子-1受体和胰岛素样生长因子结合蛋白3的多效作用

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MicroRNAs (miRs) have a major role in the pathogenesis of hepatocellular carcinoma (HCC). As the insulin-like growth factor (IGF) axis is a highly tumorigenic pathway in HCC, the present study attempted to target it with miRs. Potential targeting of crucial members of the IGF axis by miRNAs at the 3-untranslated region (3-UTR) was predicted using bioinformatic tools, such as microrna.org, Diana lab and Targetscan, while 5-UTR targeting was predicted using bibiserv software. Expression profiling of obtained miRNAs was performed using quantitative polymerase chain reaction (qPCR) in 22 non-metastatic HCC biopsy samples and 10 healthy tissues. To investigate the impact of miRNAs on their potential downstream targets, transfection of miRNAs was performed in HuH-7 cells and the targets' expression was quantified using qPCR. Transcripts of insulin-like growth factor-1 receptor (IGF-1R), insulin-like growth factor binding protein-3 (IGFBP-3) and IGF-II were found to be potentially targeted at the 5-UTR and 3-UTR regions by the single clustered hepatic metastamiRs miR-96-5p and miR-182-5p. The two miRNAs showed a similar expression pattern in HCC tissues compared to those in healthy tissues. Forced expression of miR-96-5p and miR-182-5p in the HCC cell line HuH-7 had inducing effects on IGFBP-3 and IGF-II transcripts. Of note, the two miRs had differential effects on IGF-1R, where miR-96-5p induced IGF-1R mRNA expression and miR-182-5p inhibited its expression. The present study revealed the pleio-tropic impact of the single clustered hepatic metastamiRs miR-96-5p and miR-182-5p on IGF-1R, and an inducing effect on IGF-II and IGFBP-3 in hepatocellular carcinoma.
机译：MicroRNA（miRs）在肝细胞癌（HCC）的发病机理中起主要作用。由于胰岛素样生长因子（IGF）轴在HCC中是高度致瘤的途径，因此本研究试图用miRs靶向它。使用生物信息学工具（例如microrna.org，Diana lab和Targetscan）预测了miRNA在3非翻译区（3-UTR）对IGF轴关键成员的潜在靶向，而使用bibiserv软件预测了5-UTR靶向。使用定量聚合酶链反应（qPCR）在22个非转移性HCC活检样品和10个健康组织中进行获得的miRNA的表达谱分析。为了研究miRNA对它们潜在的下游靶标的影响，在HuH-7细胞中转染了miRNA，并使用qPCR定量了靶标的表达。发现胰岛素样生长因子-1受体（IGF-1R），胰岛素样生长因子结合蛋白-3（IGFBP-3）和IGF-II的转录本可能靶向5-UTR和3-UTR区通过单簇肝转移瘤miR-96-5p和miR-182-5p。与健康组织相比，这两种miRNA在HCC组织中显示出相似的表达模式。 miR-96-5p和miR-182-5p在HCC细胞系HuH-7中的强制表达对IGFBP-3和IGF-II转录本具有诱导作用。值得注意的是，这两个miR对IGF-1R具有不同的作用，其中miR-96-5p诱导IGF-1R mRNA表达，而miR-182-5p抑制其表达。本研究揭示了单簇肝转移瘤miR-96-5p和miR-182-5p对IGF-1R的多效性，以及对肝细胞癌中IGF-II和IGFBP-3的诱导作用。

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