Inflammatory microRNAs in liver cancer

肝癌中的炎症性 microRNA

• 批准号: 230854839
• 负责人: Professor Dr. Frank Lammert
• 金额: --
• 依托单位: Signal Transduction Laboratory
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/230854839?language=en
• 关键词: Inflammatory; microRNAs; liver; cancer

Chronic inflammation is one of the hallmarks of cancer. Hepatocellular carcinoma (HCC), responsible for > 0.5 million deaths worldwide per annum, is closely related to chronic inflammation, commonly caused by hepatitis B or C virus infections or steatohepatitis. Interleukin-6, an inflammatory cytokine, which signals via Jak/STAT3, often shows increased activity in HCC. In addition, expression levels of certain miRNAs (small non-coding RNAs, which negatively regulate gene expression) are also altered in HCC and other cancers. Here, we aim to investigate the role of miRNAs in the regulation of IL-6/Jak/STAT3 signalling in hepatoma cells and non-transformed hepatocytes. We will not only study intracellular miRNAs, but will pay special attention to secreted miRNAs, isolated from blood samples. Potential targets of selected miRNAs shall be identified by detailed analysis and validation of corresponding mRNA expression data. In an independent approach, we will study miRNAs targeting key players of the IL-6 signal transduction cascade (e.g. STAT3, SOCS3). Results obtained with cell lines will be translated to samples from HCC patients (blood, tumour tissue, surrounding liver tissue) and to primary hepatocytes isolated from these patients. The project will increase our knowledge on the relevance of intracellular and secreted miRNAs in inflammatory signal transduction. We expect moreover that our approach will lead to the identification of (a) miRNAs, which could be targeted therapeutically to modulate IL-6/STAT3 signal transduction and (b) miRNAs, which may be eventually used as biomarkers in the diagnosis and prognosis of HCC. This would be most useful in the surveillance of risk patients with chronic hepatitis or liver cirrhosis to better predict potential progression into HCC at an early stage when treatment success rates are still favourable.

慢性炎症是癌症的标志之一。肝细胞癌（HCC）每年导致全球超过50万人死亡，与慢性炎症密切相关，通常由B型或C型肝炎病毒感染或脂肪性肝炎引起。白细胞介素-6是一种炎症细胞因子，通过Jak/STAT 3进行信号传导，通常在HCC中显示出增加的活性。此外，某些miRNA（小的非编码RNA，负调控基因表达）的表达水平也在HCC和其他癌症中改变。在这里，我们的目的是研究在肝癌细胞和非转化肝细胞中的IL-6/Jak/STAT 3信号转导的调节中的作用。我们将不仅研究细胞内的miRNA，但将特别关注分泌的miRNA，从血液样本中分离。通过详细分析和验证相应的mRNA表达数据，确定所选miRNA的潜在靶点。在一个独立的方法中，我们将研究靶向IL-6信号转导级联的关键参与者（例如STAT 3，SOCS 3）的miRNA。细胞系获得的结果将转化为HCC患者的样本（血液、肿瘤组织、周围肝组织）和从这些患者中分离的原代肝细胞。该项目将增加我们对细胞内和分泌的miRNAs在炎症信号转导中的相关性的了解。此外，我们期望我们的方法将导致鉴定（a）miRNA，其可以在治疗上靶向调节IL-6/STAT 3信号转导，以及（B）miRNA，其可以最终用作HCC诊断和预后中的生物标志物。这在慢性肝炎或肝硬化风险患者的监测中最有用，以便在治疗成功率仍然有利的早期阶段更好地预测潜在的HCC进展。

项目成果

Role of microRNAs in signal transduction pathways of the inflammatory cytokine interleukin-6 in hepatocellular carcinoma cell lines and primary hepatocytes

microRNA在肝细胞癌细胞系和原代肝细胞炎症细胞因子白细胞介素6信号转导通路中的作用

• DOI: 10.1016/s0959-8049(16)61630-1
• 发表时间: 2016
• 期刊: European Journal of Cancer
• 影响因子: 8.4
• 作者: Servais;M. Kirchmeyer;M. Casper;M. Hamdorf;C. Haan;P. Nazarov;L. Vallar;C. Rubie;M. Glanemann;F. Lammert;S. Kreis;I. Behrmann
• 通讯作者: I. Behrmann

ID: 194: Role of microRNAs in signal transduction pathways of the inflammatory cytokine Interleukin-6: Relevance for liver diseases

ID：194：microRNA 在炎症细胞因子 Interleukin-6 信号转导途径中的作用：与肝脏疾病的相关性

• DOI: 10.1016/j.cyto.2015.08.198
• 期刊: Cytokine
• 影响因子: 3.8
• 作者: Servais;M. Kirchmeyer;M. Hamsdorf;C. Haan;M. Casper;F. Lammert;P. Nazarov;L. Vallar;S. Kreis;I. Behrmann
• 通讯作者: I. Behrmann

ID: 202: IL-27 elicits responses similar to Interferon-gamma in non-hematopoietic cells

ID：202：IL-27 在非造血细胞中引发类似于干扰素-γ 的反应

• DOI: 10.1016/j.cyto.2015.08.206
• 期刊: Cytokine
• 影响因子: 3.8
• 作者: Rolvering;A. Zimmer;I. Behrmann;C. Haan
• 通讯作者: C. Haan

Cytokines and hepatocellular carcinoma: Potential progression markers and cell typespecific modulators of the mirnome (Interleukin-6 and JAK/STAT activating cytokines)

细胞因子和肝细胞癌：微小组的潜在进展标记物和细胞类型特异性调节剂（Interleukin-6 和 JAK/STAT 激活细胞因子）

• DOI: 10.1055/s-0036-1597466
• 发表时间: 2016
• 期刊: Zeitschrift für Gastroenterologie
• 作者: Kirchmeyer;F. A. Servais;M. Hamdorf;C. Haan;P. Nazarov;L. Vallar;M. Casper;M. Glanemann;A. Arslanow;C. Rubie;F. Lammert;S. Kreis;I. Behrmann
• 通讯作者: I. Behrmann

Evaluation der pro-steatotischen Genvariante rs641738 im MBOAT7-Gen bei Patienten mit hepatozellulärem Karzinom (HCC)

肝细胞癌 (HCC) 患者 MBOAT7 基因中促脂肪变性基因变异 rs641738 的评估

• DOI: 10.1055/s-0036-1597467
• 发表时间: 2016
• 期刊: Zeitschrift für Gastroenterologie
• 作者: Casper;M. Krawczyk;I. Behrmann;M. Glanemann;F. Lammert
• 通讯作者: F. Lammert