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）每年在全球范围内造成50万人死亡，与慢性炎症密切相关，这通常是由乙型肝炎或C病毒感染或脂肪性肝炎引起的。白介素-6（一种通过JAK/STAT3发出信号的炎性细胞因子，通常显示出HCC的活性增加。另外，在HCC和其他癌症中，某些miRNA（负调节基因表达的小型非编码RNA）的表达水平也会改变。在这里，我们旨在研究miRNA在肝癌细胞和未转化的肝细胞中IL-6/JAK/STAT3信号调节中的作用。我们不仅会研究细胞内miRNA，而且还将特别注意从血液样本中分离出来的分泌的miRNA。选定的miRNA的潜在靶标应通过详细分析和相应mRNA表达数据的验证来识别。在一种独立的方法中，我们将研究针对IL-6信号转导级联的主要参与者的miRNA（例如STAT3，SOCS3）。用细胞系获得的结果将转化为来自HCC患者（血液，肿瘤组织，周围肝组织）的样本，并将其转化为与这些患者分离的原发性肝细胞。该项目将增加我们对细胞内和分泌的miRNA在炎症信号转导中相关性的了解。此外，我们预计我们的方法将导致（a）miRNA的鉴定，可以将其靶向以治疗来调节IL-6/STAT3信号转导和（b）miRNA，最终可以用作HCC诊断和预后的生物标志物。这对于监测慢性肝炎或肝肝硬化的风险患者的监测最有用，可以更好地预测治疗成功率仍然有利的早期阶段的潜在进展到HCC。

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

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

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

Variant PNPLA3 increases the HCC risk: prospective study in patients treated at the Saarland University Medical Center

PNPLA3 变异体增加 HCC 风险：针对萨尔大学医学中心治疗患者的前瞻性研究

• DOI: 10.1055/s-0042-106308
• 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